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WO2025198366A1 - Nouveau biomarqueur de pronostic de lichen plan buccal et ses utilisations - Google Patents

Nouveau biomarqueur de pronostic de lichen plan buccal et ses utilisations

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Publication number
WO2025198366A1
WO2025198366A1 PCT/KR2025/003655 KR2025003655W WO2025198366A1 WO 2025198366 A1 WO2025198366 A1 WO 2025198366A1 KR 2025003655 W KR2025003655 W KR 2025003655W WO 2025198366 A1 WO2025198366 A1 WO 2025198366A1
Authority
WO
WIPO (PCT)
Prior art keywords
uniprot accession
protein
prognosis
lichen planus
group
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/KR2025/003655
Other languages
English (en)
Korean (ko)
Inventor
이지은
김인영
박현미
김태희
황경균
윤필영
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.)
Industry University Cooperation Foundation IUCF HYU
Bundang Hospital Seoul National University
Original Assignee
Industry University Cooperation Foundation IUCF HYU
Bundang Hospital Seoul National University
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 Industry University Cooperation Foundation IUCF HYU, Bundang Hospital Seoul National University filed Critical Industry University Cooperation Foundation IUCF HYU
Publication of WO2025198366A1 publication Critical patent/WO2025198366A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6848—Methods of protein analysis involving mass spectrometry
    • G01N33/6851—Methods of protein analysis involving laser desorption ionisation mass spectrometry
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • 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
    • C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
    • 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

  • BPIFA1 BPI Fold Containing Family A Member 1, UniProt accession No. Q9NP55
  • ISG15 Ubiquitin-like protein ISG15, UniProt accession No. P05161
  • APOBEC3B DNA dC->dU-editing enzyme APOBEC-3B, UniProt accession No. Q9UH17
  • STAT1 Signal Transducer And Activator Of Transcription 1-alpha/beta, UniProt accession No. P42224
  • WARS1 Tryptophan--tRNA ligase, cytoplasmic, UniProt accession No.
  • NUCB2 Nucleobindin-2, UniProt accession No. P80303
  • NUCB1 Nucleobindin-1, UniProt accession No. Q02818)
  • FOLH1 Glutamate carboxypeptidase 2, UniProt accession No. Q04609
  • FAM3D Protein FAM3D, UniProt accession No. Q96BQ1
  • CPD Carboxypeptidase D, UniProt accession No. O75976).
  • composition for predicting the prognosis of oral lichen planus comprising an agent capable of measuring the expression level of any one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD, or a gene encoding the same.
  • the agent capable of measuring the expression level of the protein may be an antibody or an antigen-binding fragment thereof that specifically binds to the protein; or an aptamer that specifically binds to the protein.
  • the agent capable of measuring the expression level of the gene may be a primer or probe that specifically binds to a nucleic acid molecule of the gene.
  • kits for confirming the prognosis of oral lichen planus comprising any one of the prognostic predictive compositions.
  • a method for providing information for predicting the prognosis of oral lichen planus comprising the step of measuring the expression level of any one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the same, from a biological sample isolated from a subject.
  • proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the same, from a biological sample isolated from a subject.
  • the method may further include a step of measuring the expression level of one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the same, from a biological sample isolated from a control group; and a step of comparing the expression levels of the proteins or the gene encoding the same in the subject and the control group.
  • proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the
  • any one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3 and ARF3 or a gene encoding the same of the subject is higher than that of the control group, it may be predicted that the prognosis of the subject is poor.
  • any one or more proteins selected from the group consisting of PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the same of the subject is higher than that of the control group, it can be predicted that the subject has a good prognosis.
  • the biological sample may be saliva.
  • Figure 1 is a schematic diagram showing a sample collection method and analysis method in the present invention.
  • Figure 2 shows a graph of the high pH fraction of a TMT labeled sample (x-axis: time (min), y-axis: absorbance (normalized intensity)).
  • the present inventors collected saliva samples from a group of patients with oral lichen planus, performed the same analysis as on samples from a control group that received treatment, and identified proteins that were significantly higher or lower expressed in the samples from the patient group with oral lichen planus compared to the samples from the control group, and completed and provided the invention of a biomarker and a composition for predicting the prognosis of oral lichen planus or confirming the pathological condition.
  • BPIFA1 BPI Fold Containing Family A Member 1, UniProt accession No. Q9NP55
  • ISG15 Ubiquitin-like protein ISG15, UniProt accession No. P05161
  • APOBEC3B DNA dC->dU-editing enzyme APOBEC-3B, UniProt accession No. Q9UH17
  • STAT1 Signal Transducer And Activator Of Transcription 1-alpha/beta, UniProt accession No. P42224
  • WARS1 Tryptophan--tRNA ligase, cytoplasmic, UniProt accession No.
  • VPS11 Voluolar protein sorting-associated protein 11 homolog, UniProt accession No. Q9H270
  • MX1 Interferon-induced GTP-binding protein Mx1, UniProt accession No. P20591
  • SSR1 Translocon-associated protein subunit alpha, UniProt accession No. P43307
  • TMED2 Transmembrane emp24 domain-containing protein 2, UniProt accession No. Q15363
  • UBA7 Ubiquitin-like modifier-activating enzyme 7, UniProt accession No. P41226)
  • NCSTN Nicastrin, UniProt accession No. Q92542
  • STX3 Setaxin-3, UniProt accession No.
  • ARF3 ADP-Ribosylation Factor 3, UniProt accession No. P61204
  • PRH1/2 Salivary acidic proline-rich phosphoprotein 1/2, UniProt accession Nos. P02810/P04278 for PRH1 and PRH2 respectively
  • TFF3 Trefoil Factor 3, UniProt accession No. Q07654
  • CPE Carboxypeptidase E, UniProt accession No. P16870
  • SAA1 Seerum Amyloid A1 protein, UniProt accession No. P0DJI8
  • NUCB2 Nucleobindin-2, UniProt accession No.
  • NUCB1 Nucleobindin-1, UniProt accession No. Q028178
  • FOLH1 Glutamate carboxypeptidase 2, UniProt accession No. Q04609
  • FAM3D Protein FAM3D, UniProt accession No. Q96BQ1
  • CPD Carboxypeptidase D, UniProt accession No. O75976.
  • 'prognosis' means determining whether an individual has not yet been diagnosed or has recurrence, metastasis, drug response, resistance, treatment progress, pathological condition, etc. before/after treatment.
  • the biomarkers were derived by comparing a patient group that did not receive treatment and a treatment group that did receive treatment, and the invention was completed by confirming that the biomarkers that were predominantly expressed in the patient group were indicators closer to a pathological condition.
  • one of the most preferable examples in which the present invention can be utilized is to confirm the expression level of the biomarkers in a patient group that has already been diagnosed with or is being treated for oral lichen planus and to establish a treatment strategy based on whether the expression level is 1.5 times or more higher or lower than that of the control group, or whether the expression level of the biomarkers decreases or increases over time, or to use it as a histological marker that can quantitatively confirm whether appropriate treatment is being carried out, or to use it to distinguish it from other oral diseases with similar symptoms.
  • biomarker generally includes all organic biomolecules such as polypeptides, proteins, nucleic acids, genes, lipids, glycolipids, glycoproteins, and sugars that can be detected in biological samples and that can detect biological changes.
  • the above prognosis refers to the prognosis of oral lichen planus.
  • the term ‘(bio)marker for predicting prognosis, (bio)marker for determining prognosis or prognostic marker’ means a marker including an agent capable of distinguishing the level of organic biomolecules such as polypeptides or nucleic acids (e.g., mRNA, etc.), lipids, glycolipids, glycoproteins, sugars (monosaccharides, disaccharides, oligosaccharides, etc.) that show an increase or decrease in the saliva of a patient group compared to a treated group, or a composition included therein, which can determine whether the pathological condition of oral lichen planus is improved, from normal cells or can measure the level thereof.
  • organic biomolecules such as polypeptides or nucleic acids (e.g., mRNA, etc.), lipids, glycolipids, glycoproteins, sugars (monosaccharides, disaccharides, oligosaccharides, etc.) that show an increase or decrease in the saliva of a patient group
  • composition for predicting the prognosis of oral lichen planus comprising an agent capable of measuring the expression level of any one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD, or a gene encoding the same.
  • measuring expression level in this specification refers to measuring the presence, expression, or expression level of a specific protein (peptide) or a gene encoding the protein, and specifically, may be measuring the expression level of one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D, and CPD, or mRNA or genes encoding the same.
  • proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D, and CPD, or mRNA or genes encoding the
  • the agent capable of measuring the expression level of the protein may be an antibody or an antigen-binding fragment thereof that specifically binds to the protein; or an aptamer that specifically binds to the protein.
  • antibody refers to a specific immunoglobulin directed against an antigenic site.
  • the antibody can specifically bind to one or more proteins or fragments thereof selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D, and CPD.
  • the fragment refers to a protein fragment having one or more epitopes that can be recognized by an antibody against the protein, and may be, for example, an immunogenic fragment.
  • the form of the antibody includes a polyclonal antibody, a monoclonal antibody, or a recombinant antibody, and includes all immunoglobulin antibodies. Additionally, the above antibodies include special antibodies such as humanized antibodies.
  • ELISA enzyme linked immunosorbent assay
  • RIA radioimmunoassay
  • sandwich assay Western blotting on polyacrylic gel
  • immunoblotting Western blotting on polyacrylic gel
  • antibody fragment refers to a polypeptide that does not have the structure of an intact antibody, peptide, or protein, but has a specific antigen-binding site or binding domain directed against an antigenic site.
  • the fragment includes a functional fragment of an antibody molecule other than a complete antibody having two light chains and two heavy chains.
  • a functional fragment of an antibody molecule means a fragment that retains at least an antigen-binding function, and may be Fab, F(ab'), F(ab')2, or Fv.
  • the binding fragment may comprise at least 7 amino acids, for example, 9 amino acids, or 12 amino acids.
  • Analysis methods for detecting the above protein include, but are not limited to, Western blot, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, immunoassay, immunohistochemistry assay, immunoprecipitation assay, complement fixation assay, flow cytometry (Fluorescence Activated Cell Sorter, FACS), protein chip, etc.
  • ELISA enzyme linked immunosorbent assay
  • RIA radioimmunoassay
  • Ouchterlony immunodiffusion Ouchterlony immunodiffusion
  • rocket immunoelectrophoresis tissue immunostaining
  • immunoassay immunohistochemistry assay
  • immunoprecipitation assay immunoprecipitation assay
  • complement fixation assay complement fixation assay
  • flow cytometry Fluorescence Activated Cell Sorter, FACS
  • protein chip etc.
  • the agent capable of measuring the expression level of the gene may be a primer or probe that specifically binds to the nucleic acid molecule of the gene.
  • an analysis method for example, one or more methods selected from the group consisting of reverse transcription polymerase reaction (RT-PCR), competitive reverse transcription polymerase reaction (Competitive RT-PCR), real-time reverse transcription polymerase reaction (Realtime RT-PCR), RNase protection assay (RPA), Northern blotting, and DNA chips may be used.
  • primer refers to a nucleic acid sequence having a free 3' hydroxyl group, which can form base pairs with a template complementary to a specific base sequence and serves as a starting point for copying the template strand.
  • the primer can initiate DNA synthesis in the presence of a reagent for polymerization (i.e., DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates in an appropriate buffer and temperature.
  • a reagent for polymerization i.e., DNA polymerase or reverse transcriptase
  • PCR amplification is performed using sense and antisense primers having sequences of 7 to 50 nucleotides as specific primers for a gene or mRNA encoding one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D, and CPD, and by measuring the amount of the desired product produced, it is possible to determine whether an individual has a pathological condition related to oral lichen planus or to predict the progression of the pathological condition.
  • the lengths of the sense and antisense primers can be appropriately selected according to techniques known in the art.
  • the above primers may have 10 to 100, 15 to 100, 10 to 80, 10 to 50, 10 to 30, 10 to 20, 15 to 80, 15 to 50, 15 to 30, 15 to 20, 20 to 100, 20 to 80, 20 to 50, or 20 to 30 nt.
  • probe in this specification refers to a nucleic acid fragment such as RNA or DNA that can specifically bind to a target nucleic acid, for example, mRNA, and may be labeled so as to enable detection of the presence, content, and expression level of a specific mRNA.
  • the probe may be produced in the form of an oligonucleotide probe, a single-stranded DNA probe, a double-stranded DNA probe, an RNA probe, etc.
  • the expression level of mRNA can be measured through the degree of hybridization, thereby determining whether an individual is in a pathological state related to oral lichen planus or predicting the progression of the pathological state.
  • the selection of an appropriate probe and hybridization conditions can be appropriately selected according to techniques known in the art.
  • the probe may have 10 to 100, 15 to 100, 10 to 80, 10 to 50, 10 to 30, 10 to 20, 15 to 80, 15 to 50, 15 to 30, 15 to 20, 20 to 100, 20 to 80, 20 to 50, or 20 to 30 nt.
  • the method may further include a step of measuring the expression level of one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the same, from a biological sample isolated from a control group; and a step of comparing the expression levels of the proteins or the gene encoding the same in the subject and the control group.
  • proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the
  • control group in this specification may preferably be a group that does not exhibit a pathological condition related to oral lichen planus, and most preferably may be a group of oral lichen planus patients whose pathological condition has improved through appropriate treatment commonly performed in the art.
  • any one or more proteins selected from the group consisting of BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3 and ARF3 or a gene encoding the same of the subject is higher than that of the control group, preferably higher by 1.5 times or more, it may be predicted or determined that the prognosis of the subject is poor.
  • any one or more proteins selected from the group consisting of PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D and CPD or a gene encoding the same of the subject is higher than that of the control group, preferably lower by 0.66 times or less, it may be predicted or determined that the prognosis of the subject is good.
  • Saliva samples were collected from 11 patients with oral lichen planus and 10 patients in the oral lichen planus treatment group at Seoul National University Bundang Hospital (IRB No. B-2103-675-301). The treatment group was selected after clinically confirming symptom improvement after gargling with 5-10 cc of 0.05% dexamethasone solution twice daily for 5 minutes for 4 weeks. After spitting to remove mucus and foreign substances from the oral cavity, the gargle was gargled with 10 mL of distilled water for 1 minute. The spit-out gargle was used as a saliva sample. cOmplete, Mini EDTA-free protease inhibitor cocktail (Roche) was added as a protease inhibitor to prevent protein degradation or modification in the saliva samples. After adding the inhibitor to each sample to a final concentration of 1.5X, the samples were stored at -80°C until use in the experiment.
  • FIG. 1 illustrates a schematic diagram of the experimental process for protein biomarker discovery using saliva samples.
  • Example 3 Sample preparation and in-solution digestion for mass spectrometry
  • Example 1 For mass spectrometry, 11 patient samples and 10 individual samples from the treatment group collected in Example 1 were prepared into 200 ⁇ g samples based on the results of the protein concentration measurement described above, concentrated to 100 ⁇ L, and then added to the samples to make 8 M urea and 2 M thiourea. After reducing disulfide bonds at 37°C using 0.5 ⁇ mol of TCEP (tris(2-carboxyethyl)phosphine), alkylation was performed using 1 ⁇ mol of IAA (2-iodoacetamide) in a dark environment at 25°C. After that, 25 mM ammonium bicarbonate was further added to 8 M urea to make 1 M urea.
  • TCEP tris(2-carboxyethyl)phosphine
  • LysC Endoproteinase Lys-C
  • trypsin was added at a ratio of 1:50 and digested overnight at 25°C.
  • the peptide was purified using a SepPak® tC18 cartridge (Sep-Pak tC18 1cc Vac cartridge, 100mg, Waters) and dried by vacuum drying. The dried peptide was dissolved in 100 mM tetraethylammonium bromide (TEAB) and the peptide was quantified at a ratio of 1:25.
  • TEAB tetraethylammonium bromide
  • TMT labeling reagent (Thermo Fisher Scientific) was dissolved in 80 ⁇ L of acetonitrile, and 36 ⁇ L of TMT labeling reagent was added to each sample prepared in Example 3, 42 ⁇ g of peptide sample. The reaction mixture was incubated at 20°C for 1 hour to label the peptides, and then 5 ⁇ L of 5% (w/v) hydroxylamine was added and incubated at 20°C for 15 minutes to terminate the labeling reaction. The TMT-labeled samples were combined into one tube, purified using a SepPak® tC18 cartridge, and then vacuum-dried.
  • the dried sample was dissolved in 10 mM ammonium formate.
  • 500 ⁇ g of the sample was injected onto an X-Bridge peptide BEH C18 column (4.6 mm i.d. ⁇ 250 mm length; pore size 130 ⁇ ; particle size 3.5 ⁇ m, Waters Corporation, Milford, MA, USA) using Agilent 1290 Infinity liquid chromatography to perform high pH reversed-phase peptide fractionation.
  • the column was equilibrated with 100% buffer A of 10 mM ammonium formate (pH 10).
  • Buffer B was 90% acetonitrile of 10 mM ammonium formate (pH 10).
  • the operating flow rate was 0.5 mL/min under the following gradient conditions.
  • the sample was divided into 96 peptide fractions ranging from 10 to 82.5 minutes.
  • the fractionation graph is shown in Figure 2.
  • the 96 fractions were combined into 24 fractions, and the fractions were vacuum-dried.
  • the dried peptide samples were resuspended in 20.83 ⁇ L of 0.1% formic acid and dissolved.

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Abstract

La présente invention concerne une composition de biomarqueur de pronostic ou de détermination d'état pathologique de lichen plan buccal, comprenant au moins un élément choisi dans le groupe constitué par BPIFA1, ISG15, APOBEC3B, STAT1, WARS1, VPS11, MX1, SSR1, TMED2, UBA7, NCSTN, STX3, ARF3, PRH1/2, TFF3, CPE, SAA1, NUCB2, NUCB1, FOLH1, FAM3D, et CPD. Selon la présente invention, il est possible de prédire ou de déterminer l'état pathologique ou le pronostic du lichen plan buccal sur la base d'un échantillon non invasif et facilement accessible tel que la salive, et l'invention peut être utilisée pour établir des stratégies de traitement ou pour développer des agents thérapeutiques.
PCT/KR2025/003655 2024-03-22 2025-03-21 Nouveau biomarqueur de pronostic de lichen plan buccal et ses utilisations Pending WO2025198366A1 (fr)

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KR10-2024-0039743 2024-03-22
KR1020240039743A KR20250142600A (ko) 2024-03-22 2024-03-22 구강편평태선의 예후 예측을 위한 신규한 바이오마커 및 이의 용도

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