[go: up one dir, main page]

WO2025048047A1 - Composition pour le diagnostic de la radiorésistance du cancer colorectal ou pour le pronostic du cancer colorectal - Google Patents

Composition pour le diagnostic de la radiorésistance du cancer colorectal ou pour le pronostic du cancer colorectal Download PDF

Info

Publication number
WO2025048047A1
WO2025048047A1 PCT/KR2023/017592 KR2023017592W WO2025048047A1 WO 2025048047 A1 WO2025048047 A1 WO 2025048047A1 KR 2023017592 W KR2023017592 W KR 2023017592W WO 2025048047 A1 WO2025048047 A1 WO 2025048047A1
Authority
WO
WIPO (PCT)
Prior art keywords
genes
colon cancer
mrna
expression level
protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/KR2023/017592
Other languages
English (en)
Korean (ko)
Inventor
송지영
송경희
박정인
정승윤
이동현
안지연
박종국
황상구
정인수
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Korea Institute of Radiological and Medical Sciences
Original Assignee
Korea Institute of Radiological and Medical Sciences
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Korea Institute of Radiological and Medical Sciences filed Critical Korea Institute of Radiological and Medical Sciences
Publication of WO2025048047A1 publication Critical patent/WO2025048047A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57419—Specifically defined cancers of colon
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/118—Prognosis of disease development
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the present invention relates to a composition for diagnosing radiation resistance of colon cancer and applications thereof.
  • Cancer treatment methods include surgery, chemotherapy, and radiation therapy, and the importance of radiation therapy has increased recently.
  • surgery is difficult
  • cases where tumors were effectively cured with radiation therapy alone have been reported
  • tumor treatment methods using radiation are also developing year after year, so radiation therapy has become established as a method that can effectively treat tumors in the body without any particular pain or discomfort to the patient.
  • radiation therapy has become established as a method that can effectively treat tumors in the body without any particular pain or discomfort to the patient.
  • about 30-50% of cancer patients receive radiation therapy at some point during the treatment period.
  • the importance of radiation therapy in cancer treatment is also increasing.
  • Radiation therapy is commonly used to treat various types of cancer, either alone or in combination with chemotherapy.
  • the effectiveness of radiation therapy varies depending on the nature of the cancer, the patient, and whether radiation is combined with other treatments.
  • Cancers for which radiation therapy is commonly performed include uterine cancer, pharyngeal cancer, lung cancer, brain cancer, and breast cancer. Although these cancers are the main targets of radiation therapy, they often do not respond well to radiation therapy, so strategies to increase treatment efficiency are necessary. In addition, even if radiation therapy is effective and the initial response is good, relapses often occur, so it is important to establish countermeasures for recurrent cancer to increase the effectiveness of radiation therapy.
  • radiation therapy is used as an effective cancer treatment method along with surgical operation or chemical drug therapy, and is used to kill cancer cells by treating the cancerous tissue of the patient with radiation.
  • companion diagnostics which refers to approved diagnoses that can select appropriate targeted anticancer drugs and treatment methods based on systematic analysis results of recent patient personal factors.
  • Companion diagnostics can provide clear clinical grounds for prescriptions based on a doctor's diagnosis and can suggest appropriate treatment methods to patients, which can not only increase the effectiveness of cancer treatment but also reduce the misuse of targeted anticancer drugs and contribute to the soundness of national health insurance finances.
  • the companion diagnostics market is growing in treatment fields such as breast cancer, lung cancer, colon cancer, stomach cancer, and melanoma, and breast cancer and lung cancer fields are expected to lead market growth in particular.
  • Korean Patent Application No. 10-2018-0143493 discloses a technique for diagnosing radioresistant lung cancer or pancreatic cancer by measuring the expression level of PMVK protein or mRNA, but no data is provided regarding colorectal cancer cell specificity.
  • Korean Patent Application No. 10-2018-0153659 discloses a technique for diagnosing the radiation resistance of cancer cells by measuring the expression level of the ROMO1 gene or protein, but does not present a technique for more accurately diagnosing radiation resistant colon cancer using multiple markers.
  • the inventors of the present invention conducted research on radiation resistance biomarkers and discovered a novel biomarker for diagnosing radiation resistant colon cancer.
  • the biomarker can predict resistance to radiation therapy or the prognosis of radiation therapy, and is expected to be useful in the treatment of colon cancer.
  • the purpose of the present invention is to provide a composition for diagnosing radiation resistance of colon cancer.
  • the present invention aims to provide a kit for diagnosing radiation resistance of colon cancer.
  • the present invention aims to provide a method for providing information for diagnosing radioresistance of colon cancer.
  • the present invention aims to provide a composition for predicting the prognosis of radiation therapy for colon cancer.
  • the present invention aims to provide a kit for predicting the prognosis of radiation therapy for colon cancer.
  • the present invention aims to provide a method for providing information for predicting the prognosis of radiation therapy for colon cancer.
  • one aspect of the present invention provides a composition for diagnosing radiation resistance of colon cancer, comprising an agent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • kits for diagnosing radiation resistance of colon cancer comprising the composition for diagnosing radiation resistance of colon cancer.
  • another aspect of the present invention provides a method for providing information for diagnosing radioresistance of colon cancer, comprising the steps of: (a) measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes in a sample isolated from an individual, or proteins encoded by the two or more genes; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein of a normal control.
  • compositions for predicting the prognosis of radiation therapy for colon cancer comprising an agent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • kits for predicting the prognosis of radiation therapy for colon cancer comprising a composition for predicting the prognosis of radiation therapy for colon cancer.
  • Another aspect of the present invention provides a method for providing information for predicting the prognosis of radiation therapy for colon cancer, comprising the steps of: (a) measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes in a sample isolated from a subject; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein of a normal control.
  • composition for diagnosing radiation resistance of colon cancer or predicting prognosis of radiation therapy of colon cancer 1.
  • One aspect of the present invention provides a composition for diagnosing radiation resistance of colon cancer.
  • composition for diagnosing radiation resistance of colon cancer of the present invention contains, as an active ingredient, an agent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • composition for predicting the prognosis of radiation therapy for colon cancer of the present invention contains, as an active ingredient, an agent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • the CXCL5 protein refers to not only the wild-type CXCL5 protein consisting of the amino acid sequence of SEQ ID NO: 1, but also an equivalent that has a different partial sequence but has the same or similar function or activity as the wild-type CXLC5 protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 1.
  • CD68 Cluster of Differentiation 68, NCBI gene ID: 968 protein is a protein expressed in monocyte lineage cells and macrophages, and is generally known as a scavenger receptor that plays a role in removing cellular debris, promoting phagocytosis, and mediating macrophage recruitment and activation.
  • the CD68 protein refers to not only the wild-type CD68 protein consisting of the amino acid sequence of SEQ ID NO: 2, but also an equivalent that has a different sequence from the wild-type CD68 protein but has the same or similar function or activity as the wild-type CD68 protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 2.
  • MATN1 (Matrilin 1, NCBI gene ID: 4146) protein is a cartilage matrix protein that is involved in the formation of filamentous networks in the extracellular matrix of various tissues, and mutations in this gene are known to be associated with various hereditary chondrodysplasias.
  • the MATN1 protein refers to not only the wild-type MATN1 protein consisting of the amino acid sequence of SEQ ID NO: 3, but also an equivalent that has a different sequence from the wild-type MATN1 protein but has the same or similar function or activity as the wild-type MATN1 protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 3.
  • SERPING1 (Serpin family G member 1, NCBI gene ID: 710) protein is a protease inhibitor belonging to the serpin superfamily, also known as a C1 esterase inhibitor, and is known to regulate physiological pathways including complement activation, blood coagulation, fibrinolysis, and kinin production by inhibiting the activation of the C1 complex.
  • the SERPING1 protein refers to not only the wild-type SERPING1 protein consisting of the amino acid sequence of SEQ ID NO: 4, but also an equivalent that has a different sequence from the wild-type SERPING1 protein but has the same or similar function or activity as the wild-type SERPING1 protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 4.
  • SNCG Glomma-synuclein, NCBI gene ID: 6623
  • SNCG Stemma-synuclein, NCBI gene ID: 6623
  • protein is a type of synuclein family protein that is related to the pathogenesis of degenerative brain diseases and is often observed to be overexpressed in breast cancer cells, and is known to have a high correlation with the development of breast cancer.
  • the SNCG protein refers to not only the wild-type SNCG protein consisting of the amino acid sequence of SEQ ID NO: 5, but also an equivalent that has a part of the sequence different therefrom but has the same or similar function or activity as the wild-type SNCG protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 5.
  • VTN (Vitronectin, NCBI gene ID: 7448) protein is a glycoprotein of the hemopexin family synthesized in the liver. It is known to promote cell adhesion and migration by binding to integrin alpha-V beta-3 and connecting cells to the extracellular matrix, and to be involved in hemostasis as a component of platelets.
  • the VTN protein refers to not only a wild-type VTN protein consisting of an amino acid sequence of SEQ ID NO: 6, but also an equivalent that has a different sequence from the wild-type VTN protein but has the same or similar function or activity as the wild-type VTN protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 6.
  • FBXO4 (F-box protein 4, NCBI gene ID: 26272) protein is a protein-coding factor characterized by an F-box motif of about 40 amino acids, and is known to directly contribute to cell transformation, tumorigenesis, and progression by generating Fbx proteins that contain other protein-protein interaction modules or lack recognizable motifs.
  • the FBXO4 protein is a tumor suppressor, and its tumor suppression activity is reported to be associated with dysregulation of cyclin D1 protein degradation.
  • the FBXO4 protein refers to not only the wild-type FBXO4 protein consisting of the amino acid sequence of SEQ ID NO: 7, but also an equivalent that has some sequence differences but has the same or similar function or activity as the wild-type FBXO4 protein, and the equivalent may include an amino acid sequence having a sequence identity of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the amino acid sequence of SEQ ID NO: 7.
  • SYTL4 (Synaptotagmin like 4, NCBI gene ID: 94121) protein has an N-terminal Rab27 binding domain and a C-terminal tandem C2 domain, which allows it to bind to Rab GTPases and participate in intracellular membrane trafficking, and is known to regulate the release of nucleolar granules into cells or the secretion of pancreatic and pituitary hormones.
  • the SYTL4 protein refers to not only the wild-type SYTL4 protein consisting of the amino acid sequence of SEQ ID NO: 8, but also an equivalent that has some sequence differences but has the same or similar function or activity as the wild-type SYTL4 protein, and the equivalent may include an amino acid sequence having a sequence homology of about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more to the amino acid sequence of SEQ ID NO: 8.
  • composition for diagnosing radiation resistance of colon cancer may contain, as an active ingredient, an agent for measuring the expression level of mRNA of two genes, three genes, four genes, five genes, six genes, seven genes, or eight genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 genes, or proteins encoded by the above genes.
  • composition for predicting the prognosis of radiation therapy for colon cancer may contain, as an active ingredient, an agent for measuring the expression level of mRNA of two genes, three genes, four genes, five genes, six genes, seven genes, or eight genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 genes, or proteins encoded by the above genes.
  • mRNA of a gene selected from the group consisting of the CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by the genes have differential expression levels in radiation-resistant and -sensitive colon cancer cells and have a close correlation with a decrease in the survival rate of colon cancer patients.
  • the formulation for measuring the expression level of mRNA of one or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes of the present invention or a protein encoded by one or more genes can diagnose the radioresistance of colon cancer more effectively than mRNA of other genes and/or proteins encoded by the genes and combinations thereof, and can predict the prognosis of radiation therapy for colon cancer, thereby determining whether to perform radiation therapy and the optimal dose of radiation therapy, thereby improving the efficiency and treatment results of radiation therapy for colon cancer.
  • the expression of the genes CXCL5, CD68, MATN1, SERPING1, SNCG and VTN is upregulated by radiation exposure, and the expression of the genes FBXO4 and SYTL4 is downregulated.
  • the CXCL5, CD68 and MATN1 genes are up-regulated in their expression in radioresistant colon cancer cells
  • the SERPING1, SNCG and VTN genes are up-regulated in their expression in radiosensitive colon cancer cells.
  • the CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 genes may be genes whose expression is upregulated, thereby decreasing the survival rate of colon cancer patients.
  • the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG and VTN genes or the expression level of proteins encoded by two or more genes is high compared to the normal control group, it can be determined that radioresistance is present, and if it is low, it can be determined that radioresistance is low or radiosensitivity is present.
  • radioresistance can be determined to be high, and if the mRNA of two to six genes and/or the two to six proteins encoded by the genes are all lowly expressed, radioresistance can be determined to be low.
  • the expression levels of mRNA of the FBXO4 and SYTL4 genes or the proteins encoded by the genes are lower than those of the normal control group, it can be determined that radioresistance exists, and if they are higher, it can be determined that radioresistance is low or radiosensitivity exists.
  • the prognosis of radiation therapy for colon cancer can be determined to be negative, and if the expression level is low, the prognosis of radiation therapy for colon cancer can be determined to be positive.
  • the prognosis of radiation therapy for colon cancer can be determined to be negative, and if the mRNA of two to six genes and/or the two to six proteins encoded by the genes are all lowly expressed, the prognosis of radiation therapy for colon cancer can be determined to be positive.
  • the prognosis of radiation therapy for colon cancer can be judged to be negative, and when the expression levels are high, the prognosis of radiation therapy for colon cancer can be judged to be positive.
  • composition for diagnosing radiation resistance of colon cancer and the composition for predicting the prognosis of radiation therapy for colon cancer of the present invention may include an agent for measuring the expression level of mRNA of the SERPING1 or SNCG gene or a protein encoded by the gene.
  • radio-resistance means a state in which a substance is not easily affected by radiation exposure and there is little change in cell recovery or proliferation when exposed to radiation.
  • radio-sensitive means a state in which a substance is easily affected by radiation exposure and there is a change in cell recovery or proliferation when exposed to radiation.
  • radiation therapy means treating cancer through a mechanism of inducing apoptosis of cancer cells by inhibiting cell division through DNA damage of cancer cells by irradiating them with radiation.
  • the radiation therapy can be performed alone or in combination with surgical treatment, or as a combination therapy with anticancer chemotherapy or a radiation sensitizer, for the curative, adjuvant, or palliative purposes of solid cancer.
  • colorectal cancer may include colon cancer, rectal cancer, etc.
  • diagnosis includes determining the susceptibility of an individual to a particular disease or condition, determining whether an individual currently has a particular disease or condition, determining the prognosis of an individual with a particular disease or condition, or therametrics (e.g., monitoring the condition of an individual to provide information about the efficacy of a treatment).
  • prognosis means an outlook or preliminary evaluation of the medical outcome of a disease, and includes a positive prognosis (positive prognosis) or a negative prognosis (negative prognosis).
  • the positive prognosis includes improvement or stabilization of the disease, such as a state of no disease, tumor regression, long-term survival possibility, or disease-free survival rate
  • the negative prognosis includes progression or mortality of the disease, such as decreased survival rate, recurrence, tumor growth, metastasis, and drug resistance.
  • prediction means to guess in advance about the medical outcome, such as the course of a disease (progression, improvement, recurrence, tumor growth, possibility of death or survival after drug resistance treatment, etc.) or responsiveness to treatment such as chemotherapy or radiation therapy.
  • the diagnosis may be a diagnosis of radiation resistance of colon cancer
  • the prognosis prediction may be a prognosis prediction of radiation treatment of colon cancer
  • measurement of the mRNA expression level means a process of confirming the presence and expression level of mRNA of the gene in a biological sample for the purpose of diagnosing the radiation resistance of colon cancer and/or predicting the prognosis of radiation treatment of colon cancer.
  • a primer, a probe, or an antisense nucleotide that specifically binds to the gene or mRNA can be used, and the measurement of the expression level of the mRNA can be performed by one or more methods selected from the group consisting of RT-PCR, competitive RT-PCR, real-time RT-PCR, RNase protection assay (RPA), Northern blotting, and DNA chips, but is not limited thereto.
  • the measurement of the protein expression level means a process of confirming the presence and expression level of the protein in a biological sample for the diagnosis of radiation resistance of colon cancer and/or prediction of the prognosis of radiation treatment of colon cancer, and a polypeptide, compound, antibody or aptamer capable of specifically binding to the protein may be used as an agent for measuring the expression level of the protein, and the measurement of the expression level of the protein may be performed by Western blotting, ELISA (enzyme linked immunosorbent assay), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, dual luciferase reporter assay, immunoprecipitation assay, complement fixation assay, FACS (fluorescence activated cell sorter) and protein It can be performed by one or more methods selected from the group consisting of chips, but is not limited thereto.
  • Non-limiting examples of such modifications include methylation, capping, substitution of one or more of the natural nucleotides with their analogues, and modifications between nucleotides, such as modification with uncharged linkers (e.g., methyl phosphonate, phosphotriester, phosphoroamidate, carbamate, etc.) or charged linkers (e.g., phosphorothioate, phosphorodithioate, etc.).
  • uncharged linkers e.g., methyl phosphonate, phosphotriester, phosphoroamidate, carbamate, etc.
  • charged linkers e.g., phosphorothioate, phosphorodithioate, etc.
  • the nucleic acids may contain one or more additional covalently bonded moieties, such as proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.), intercalators (e.g., acridine, psoralen, etc.), chelating agents (e.g., metals, radioactive metals, iron, oxidizing metals, etc.), and alkylating agents.
  • the primers of the present invention may be modified with labels that can directly or indirectly provide a detectable signal, such as radioisotopes, fluorescent molecules, biotin, etc.
  • the term "probe” refers to a nucleic acid capable of complementarily binding to mRNA of several to several hundred bases in length, which is produced through an enzymatic chemical separation and purification process or a synthetic process.
  • the probe of the present invention is a probe capable of complementarily binding to the biomarker gene or mRNA of the present invention, and can confirm the presence or absence of mRNA by labeling it with a radioactive isotope or enzyme, and can be designed and modified by a known method and used.
  • the "antisense nucleotide” refers to DNA, RNA or a derivative thereof containing a nucleic acid sequence complementary to the sequence of a specific mRNA, which binds to the complementary sequence in the mRNA and inhibits the translation of the mRNA into a protein.
  • the sequence of the antisense nucleotide refers to a DNA or RNA sequence that is complementary to the mRNA of the biomarker gene of the present invention and can bind to the mRNA. This can inhibit essential activities for translation, translocation into the cytoplasm, maturation or all other overall biological functions of the mRNA.
  • the antisense nucleotide can be synthesized in vitro by a conventional method and administered in vivo or the antisense nucleotide can be synthesized in vivo, and the antisense nucleotide that can be used in the present invention can be produced by a method known in the art with reference to the base sequence and/or amino acid sequence of the biomarker gene and/or protein of the present invention.
  • the "antibody” refers to a globulin-based protein that reacts when an antigen, which is a foreign substance, invades while circulating in the blood or lymph in the immune system of a living body, and means a protein that specifically binds to an antigen.
  • the antibody means an antibody that specifically binds to the biomarker protein of the present invention, and may include all of a polyclonal antibody, a monoclonal antibody, and a recombinant antibody, and includes not only a complete form having two full-length light chains and two full-length heavy chains, but also a functional fragment of an antibody molecule.
  • a functional fragment of an antibody molecule means a fragment that has at least an antigen-binding function, and includes Fab, F(ab'), F(ab') 2, and Fv, etc.
  • the antibody that specifically binds to the biomarker protein of the present invention may be produced by a known method known to those skilled in the art, and may be produced, for example, by injecting the biomarker protein, which is an immunogen, into an external host.
  • the foreign host includes mammals such as mice, rats, sheep, and rabbits, and the immunogen can be injected intramuscularly, intraperitoneally, or subcutaneously, and is usually administered together with an adjuvant to increase antigenicity. Thereafter, blood is periodically collected from the foreign host, and serum showing specificity for the antigen can be collected to isolate antibodies.
  • the "aptamer” is a single-stranded oligonucleotide, and means a nucleic acid molecule having a size of about 20 to 60 nucleotides and having binding activity to a predetermined target molecule.
  • the aptamer has various three-dimensional structures depending on the sequence, can have high affinity for a specific substance like an antigen-antibody reaction, and can inhibit the activity of a predetermined target molecule by binding to the predetermined target molecule.
  • the aptamer may be RNA, DNA, a modified nucleic acid, or a mixture thereof, and may be in a linear or cyclic form.
  • the aptamer in the present invention can specifically bind to a protein encoded by the biomarker gene of the present invention, and can be prepared by a person skilled in the art from the base sequence of the biomarker gene of the present invention by a known method.
  • Another aspect of the present invention provides a kit for diagnosing radiation resistance of colon cancer.
  • another aspect of the present invention provides a kit for predicting the prognosis of radiation therapy for colon cancer.
  • the kit for diagnosing radiation resistance of colon cancer of the present invention contains, as an active ingredient, a preparation for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • the kit for predicting the prognosis of radiation therapy for colon cancer of the present invention contains, as an active ingredient, a preparation for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • the "kit” means a tool which can diagnose the radioresistance of colon cancer or predict the prognosis of radiation therapy of colon cancer by confirming the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • the kit of the present invention may include an agent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes, specifically, a primer, a probe and an antisense nucleotide that specifically bind to the mRNA of the above genes, or a polypeptide, a compound, an antibody and an aptamer that specifically bind to the above proteins, and may include one or more other component compositions, solutions, or devices suitable for an analysis method.
  • an agent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes, specifically, a primer, a probe and an antisense nucleotide that specifically bind to the mRNA of the above genes
  • the kit may additionally include a user manual describing optimal reaction performance conditions.
  • the manual may include a guide booklet in the form of a pamphlet or leaflet, a label attached to the kit, and a description on the surface of a package containing the kit, and may include information disclosed or provided through electronic media such as the Internet.
  • the kit may be an RT-PCR kit, a microarray chip kit, a DNA kit, an ELISA kit, a protein chip kit, or a rapid kit.
  • Another aspect of the present invention provides a method for providing information for diagnosing radiation resistance of colon cancer.
  • another aspect of the present invention provides a method for providing information for predicting the prognosis of radiation therapy for colon cancer.
  • the method for providing information for diagnosing radiation resistance of colon cancer of the present invention comprises: (a) a step of measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes in a sample isolated from an individual; and (b) a step of comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein of a normal control.
  • the method for providing information for predicting the prognosis of radiation therapy for colon cancer of the present invention comprises (a) a step of measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes in a sample isolated from an individual; and (b) a step of comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein of a normal control.
  • step (a) may include a step of measuring the expression level of mRNA of the SERPING1 or SNCG gene or a protein encoded by the gene.
  • step (a) may include a step of measuring the expression level of mRNA of the SERPING1 or SNCG gene or a protein encoded by the gene.
  • step (b) when the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG and VTN genes or the protein encoded by two or more genes is compared with the expression level of mRNA or protein of a normal control group, if the expression level is higher than the expression level of the normal control group, the colon cancer can be determined to have radiation resistance.
  • the above high expression level may include that the expression level of the individual is increased by a similar level or by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% and 1000% or more compared to the expression level of a normal control.
  • the colon cancer can be determined to have radiation resistance.
  • the low expression level may include that the expression level of the subject is reduced by a similar level or 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99% or more compared to the expression level of the normal control group.
  • step (b) if the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG and VTN genes or the protein encoded by two or more genes is compared with the expression level of mRNA or protein of a normal control group and is higher than the expression level of the normal control group, the prognosis of radiation therapy for colon cancer can be determined to be negative.
  • the above high expression level may include that the expression level of the individual is increased by a similar level or by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% and 1000% or more compared to the expression level of a normal control.
  • the prognosis of the radiation therapy for colon cancer of the present invention if the expression level of the mRNA or the protein encoded by the FBXO4 and SYTL4 genes or the expression level of the protein encoded by the genes is compared with the expression level of the mRNA or the protein of the normal control group in the step (b), and if the expression level is lower than the expression level of the normal control group, the prognosis of the radiation therapy for colon cancer can be determined to be negative.
  • the low expression level may include that the expression level of the subject is similar to the expression level of the normal control group or is reduced by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99% or more.
  • the information-providing method for diagnosing radiation resistance of colon cancer of the present invention may further include: (c-1) a step of determining that the colon cancer has radiation resistance when the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN genes or proteins encoded by two or more genes is high compared to a normal control; and/or (c-2) a step of determining that the colon cancer has radiation resistance when the expression level of mRNA of FBXO4 and SYTL4 genes or proteins encoded by the above genes is low compared to a normal control.
  • the method for providing information for predicting the prognosis of radiation therapy for colon cancer of the present invention may further include: (c-1) a step of determining that the prognosis of radiation therapy for colon cancer is negative when the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN genes or proteins encoded by the two or more genes is high compared to a normal control group; and/or (c-2) a step of determining that the prognosis of radiation therapy for colon cancer is negative when the expression level of mRNA of FBXO4 and SYTL4 genes or proteins encoded by the above genes is low compared to a normal control group.
  • Another aspect of the present invention provides a method for diagnosing radioresistance of colon cancer, comprising the steps of: (a) measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes in a sample isolated from an individual, or proteins encoded by the two or more genes; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein of a normal control.
  • Another aspect of the present invention provides a use of a formulation for diagnosing radioresistance of colon cancer, the formulation comprising measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • Another aspect of the present invention provides a use of a formulation for predicting the prognosis of radiation therapy for colorectal cancer, the formulation comprising measuring the expression levels of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or proteins encoded by two or more genes.
  • mRNA of the CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes or the proteins encoded by the genes have differential expression levels in radioresistant and sensitive colon cancer cells, and are closely correlated with the decreased survival rate of colon cancer patients.
  • the agent for measuring the expression level of mRNA of a gene selected from the group consisting of the CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes of the present invention or the protein encoded by the gene can effectively diagnose the radioresistance of colon cancer or predict the prognosis of colon cancer radiotherapy, and thereby determine whether to perform radiotherapy and the optimal dose of radiotherapy, thereby improving the efficiency and treatment results of radiotherapy for colon cancer.
  • Figure 1 shows the results of radiosensitivity measurements for human colon cancer cell lines HT29 and HCT116.
  • Figure 2 shows the results of analyzing genes whose expression increased or decreased after irradiation with a dose of 8 Gy to human colon cancer cell lines HT29 and HCT116.
  • Figure 3 shows the results of analyzing the changes in protein expression of radiation-responsive genes in human colon cancer cell lines HT29 and HCT116.
  • Figure 4 shows the results of analyzing the expression levels and risk of CXCL5 and CD68 genes using the DESeq2 program for the RNAseq results (GSE107422) of 110 patients who relapsed after developing colorectal cancer.
  • Figure 5a shows Kaplan-Meier survival curves for the survival of patients with colon cancer according to VTN, SNCG, or SERPING1 expression.
  • Figure 5b shows Kaplan-Meier survival curves for the survival rate of patients with colon cancer according to the expression of VTN and MATN1, VTN and SERPING1, SNCG and SYTL4, SNCG and CD68, or SNCG and FBXO4.
  • Figure 6a shows the change in cell viability measured after knocking down the expression of radioresistance genes using siRNA in the human colon cancer cell line HCT116.
  • Figure 6b shows the change in cell viability measured after knocking down the expression of radioresistance genes using siRNA in the human colon cancer cell line HT29.
  • Example 1 Measurement of radiation sensitivity of colon cancer cell lines
  • Human colon cancer cell lines HT29 and HCT116 were purchased from ATCC (American Type Culture Collection, USA) and maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin (10,000 U/ml) at 5% CO2 and 37°C.
  • FBS fetal bovine serum
  • penicillin-streptomycin 10,000 U/ml
  • each cell line was seeded in an appropriate number of cells in a 60 mm dish, and after 24 hours, radiation was irradiated at various doses and cultured for 10-14 days under conditions of 5% CO2 and 37°C. After that, the formed cell colonies were washed with phosphate buffered saline (PBS) and stained with a 100% methanol mixture containing 1% methylene blue. The stained cell colonies (colonies with more than 50 cells) were dried at room temperature and then visually counted for each dish.
  • PBS phosphate buffered saline
  • the survival rate of the HT29 cell line after radiation exposure was measured to be significantly higher than that of the HCT116 cell line, confirming that the HT29 cell line has higher radiation resistance than the HCT116 cell line (Fig. 1).
  • genes were selected based on transcriptome results analyzed in HT29 and HCT116 cell lines, and the radiation responsiveness of each gene was measured by real-time reverse transcription polymerase chain reaction (real-time RT-PCR).
  • the primer information used in this example is as shown in Table 1 below.
  • the HT29 and HCT116 cell lines were irradiated with 0 or 8 Gy of radiation, and then the expression of each gene was measured.
  • the expression of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN was increased in both cell lines by radiation irradiation, while the expression of FBXO4 and SYTL4 was decreased in both cell lines by radiation irradiation (Fig. 2).
  • CXCL5, CD68, and MATN1 were highly expressed in the relatively radioresistant HT29 cell line, SERPING1, SNCG, and VTN were highly expressed in the relatively radiosensitive HCT116 cell line, and FBXO4 and SYTL4 were similarly expressed in both cell lines.
  • CXCL5 was highly expressed in the relatively radioresistant HT29 cell line
  • SNCG was highly expressed in the relatively radiosensitive HCT116 cell line.
  • VTN protein was significantly increased by radiation exposure, while FBXO4 protein was decreased (Fig. 3).
  • CD68, CXCL5, SNCG, and SERPING1 are all secreted proteins known to be closely related to the activation of immune cells around tumors, and thus, the decrease in the Western blot may mean that secretion into the medium has increased.
  • the risk of survival rate of colon cancer patients due to increased SNCG expression and the risk due to increased SERPING1 expression were both 1.7, which means that increased expression of SNCG and SERPING1 can confirm increased risk and decreased survival rate alone, and can be classified as a radioresistance factor.
  • the risk was found to increase further when co-expressed with CD68, SYTL4, or FBXO4 increased.
  • the risk of increased expression of VTN alone was 1.4, which was not statistically significant, and when co-expression of VTN/MATN1 or VTN/SERPING1 increased, the risk was 1.5 and 1.7, respectively, indicating a significant decrease in overall survival rate.
  • FBXO4 and SYTL4 have a decreased expression due to radiation irradiation, and when their co-expression with other gene panels increases, the overall survival period of colorectal cancer patients decreases. Therefore, colorectal cancer patients with high expression of FBXO4 and SYTL4 can be considered as candidates for radiation therapy and have a positive prognosis of radiation therapy.
  • CD68, CXCL5, MATN1, SERPING1, SNCG, and VTN have a increased expression due to radiation irradiation, and when their expression increases, they are directly linked to a decreased survival rate of colorectal cancer patients. Therefore, these genes have radiation resistance, and colorectal cancer patients with high expression of these genes can be considered as excluded candidates for radiation therapy and have a negative prognosis of radiation therapy.
  • Example 5 Analysis of cell viability by knockdown of radiation-responsive genes in human colon cancer cells
  • each siRNA was transfected into colon cancer cell lines using LipofectamineTM RNAiMAX transfection reagent (ThermoFisher scientific, USA) based on a 96-well plate, and then irradiated with 8 Gy of radiation. After 48 hours, the cell viability was measured by treating with CCK-8 (DOJINDO, Japan) reagent.
  • the siRNA information used in this example is as shown in Table 5 below.
  • SNCG/CD68/VTN co-knockdown was shown to further increase cell death compared to SNCG knockdown alone, SNCG/CD68 co-knockdown compared to CD68 knockdown alone, and SNCG/CD68/VTN co-knockdown compared to SNCG/CD68 co-knockdown (Fig. 6b).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Hospice & Palliative Care (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Genetics & Genomics (AREA)
  • General Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Dans la présente invention, l'ARNm de gènes CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 et SYTL4, ou les protéines codées par ces gènes, présentent des niveaux d'expression différentiels entre des cellules cancéreuses colorectales radiorésistantes et radiosensibles, et sont étroitement corrélés avec des taux de survie réduits chez des patients atteints d'un cancer colorectal. De ce fait, un agent permettant de mesurer les niveaux d'expression de l'ARNm des gènes sélectionnés dans le groupe constitué de CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 et SYTL4 ou des protéines codées par les gènes selon la présente invention permet de diagnostiquer efficacement la radiorésistance dans le domaine du cancer colorectal ou de pronostiquer le déroulement d'une radiothérapie dans le cas du cancer colorectal. Ceci permet de déterminer s'il faut procéder à une radiothérapie et à la dose de rayonnement optimale, ce qui permet d'améliorer l'efficacité et les résultats de radiothérapie pour le cancer colorectal.
PCT/KR2023/017592 2023-08-25 2023-11-03 Composition pour le diagnostic de la radiorésistance du cancer colorectal ou pour le pronostic du cancer colorectal Pending WO2025048047A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2023-0112012 2023-08-25
KR1020230112012A KR20250031081A (ko) 2023-08-25 2023-08-25 대장암의 방사선 저항성 진단용 또는 대장암의 예후 예측용 조성물

Publications (1)

Publication Number Publication Date
WO2025048047A1 true WO2025048047A1 (fr) 2025-03-06

Family

ID=94819832

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2023/017592 Pending WO2025048047A1 (fr) 2023-08-25 2023-11-03 Composition pour le diagnostic de la radiorésistance du cancer colorectal ou pour le pronostic du cancer colorectal

Country Status (2)

Country Link
KR (1) KR20250031081A (fr)
WO (1) WO2025048047A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200181714A1 (en) * 2016-09-19 2020-06-11 Institut Gustave-Roussy NOX2 as a Biomarker of Radiotherapy Efficiency in Cancer Patients
KR102239722B1 (ko) * 2019-10-21 2021-04-13 동국대학교 경주캠퍼스 산학협력단 암의 방사선 내성을 진단하기 위한 조성물 및 방사선 내성 암 치료용 약학적 조성물
US20210262036A1 (en) * 2020-02-14 2021-08-26 National Cheng Kung University Biomarker for prognosis of colorectal cancer
US20220008750A1 (en) * 2017-07-21 2022-01-13 Varian Medical Systems, Inc. Methods of use of ultra-high dose rate radiation and therapeutic agent
KR20220155178A (ko) * 2021-05-14 2022-11-22 한국원자력의학원 방사선 치료 예후 예측용 또는 방사선 저항성 암 진단용 바이오마커 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200181714A1 (en) * 2016-09-19 2020-06-11 Institut Gustave-Roussy NOX2 as a Biomarker of Radiotherapy Efficiency in Cancer Patients
US20220008750A1 (en) * 2017-07-21 2022-01-13 Varian Medical Systems, Inc. Methods of use of ultra-high dose rate radiation and therapeutic agent
KR102239722B1 (ko) * 2019-10-21 2021-04-13 동국대학교 경주캠퍼스 산학협력단 암의 방사선 내성을 진단하기 위한 조성물 및 방사선 내성 암 치료용 약학적 조성물
US20210262036A1 (en) * 2020-02-14 2021-08-26 National Cheng Kung University Biomarker for prognosis of colorectal cancer
KR20220155178A (ko) * 2021-05-14 2022-11-22 한국원자력의학원 방사선 치료 예후 예측용 또는 방사선 저항성 암 진단용 바이오마커 조성물

Also Published As

Publication number Publication date
KR20250031081A (ko) 2025-03-06

Similar Documents

Publication Publication Date Title
US20130042333A1 (en) Markers for cancer prognosis and therapy and methods of use
AU2020200253A1 (en) Method of diagnosis and treatment
JP2015526078A (ja) ヒト二重微小染色体２阻害剤と関連するマーカー
KR20080080525A (ko) 유전자 전사에 대한 ｆｇｆｒ３의 억제제의 효과
CN101632833B (zh) 一种前列腺癌相关的基因及其用途
WO2021177691A1 (fr) Composition pour le diagnostic ou le traitement de la résistance aux médicaments anticancéreux
WO2017026843A1 (fr) Procédé de fourniture d'informations sur la leucémie myéloïde chronique
WO2022203314A2 (fr) Composition pour le diagnostic différentiel d'une tumeur maligne des gaines nerveuses périphériques
KR102615262B1 (ko) 전립선암의 엔잘루타미드 저항성 예측용 신규 바이오마커 및 이의 용도
WO2021182843A1 (fr) Composition pour le diagnostic ou le traitement de la résistance aux médicaments anticancéreux
WO2017078318A1 (fr) Composition de biomarqueur permettant une prédiction de la sensibilité au sorafénib
WO2014014157A1 (fr) Utilisation de l'adcy3 pour diagnostiquer et traiter le cancer de l'estomac
KR102238258B1 (ko) 간암 진단을 위한 신규 바이오마커 및 이를 이용한 치료 방법
WO2025048047A1 (fr) Composition pour le diagnostic de la radiorésistance du cancer colorectal ou pour le pronostic du cancer colorectal
WO2024215053A1 (fr) Biomarqueur pour prédire la réponse au traitement du cancer du poumon et l'évaluation et le pronostic de l'efficacité
WO2022019604A1 (fr) Biomarqueur spécifique du cancer du foie et utilisation associée
WO2025048046A1 (fr) Composition pour le diagnostic de la radiorésistance dans le cadre du cancer pulmonaire ou pour le pronostic du cancer pulmonaire
WO2025063372A1 (fr) Composition pour diagnostiquer la radiosensibilité du cancer du sein ou pronostiquer un cancer du sein
WO2020166992A1 (fr) Composition pour un diagnostic du cancer
WO2022177341A1 (fr) Composition pour diagnostiquer une résistance à un agent anticancéreux
WO2021206406A1 (fr) Composition pour le diagnostic ou le traitement de la résistance aux médicaments anticancéreux
JP5209699B2 (ja) 胃癌遺伝子ＺＮＦ３１２ｂ、該遺伝子から翻訳されるタンパク質、ならびに診断キット及び該タンパク質を使用する抗癌剤スクリーニング方法
KR100861465B1 (ko) 위암 유발 유전자 ＺＮＦ312ｂ와 이에 의해 코드되는단백질 및 이를 이용한 위암 진단 키트
WO2019066263A1 (fr) Composition pharmaceutique permettant de prévenir ou de traiter une maladie dégénérative neuronale comprenant une protéine nckap1 ou un gène codant cette dernière
WO2019103456A2 (fr) Composition de biomarqueur pour diagnostiquer un cancer résistant à la radiothérapie ou pour prédire un pronostic de radiothérapie, contenant de la pmvk en tant que principe actif

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23950922

Country of ref document: EP

Kind code of ref document: A1