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WO2013002433A1 - Méthode de diagnostic du cancer du sein - Google Patents

Méthode de diagnostic du cancer du sein Download PDF

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Publication number
WO2013002433A1
WO2013002433A1 PCT/KR2011/004729 KR2011004729W WO2013002433A1 WO 2013002433 A1 WO2013002433 A1 WO 2013002433A1 KR 2011004729 W KR2011004729 W KR 2011004729W WO 2013002433 A1 WO2013002433 A1 WO 2013002433A1
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WO
WIPO (PCT)
Prior art keywords
breast cancer
thioredoxin
blood
cancer
concentration
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.)
Ceased
Application number
PCT/KR2011/004729
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English (en)
Korean (ko)
Inventor
김일한
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 Academic Cooperation Foundation of Pai Chai University
Original Assignee
Industry Academic Cooperation Foundation of Pai Chai 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 Academic Cooperation Foundation of Pai Chai University filed Critical Industry Academic Cooperation Foundation of Pai Chai University
Priority to PCT/KR2011/004729 priority Critical patent/WO2013002433A1/fr
Priority to US13/560,208 priority patent/US9382587B2/en
Publication of WO2013002433A1 publication Critical patent/WO2013002433A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • G01N33/57415—Specifically defined cancers of breast
    • 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
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals

Definitions

  • the present invention relates to a method for diagnosing breast cancer by measuring thioredoxin 1 from blood.
  • Breast cancer is a malignant tumor of the breast, and it is known that it is caused by a transition from cancer cells to epithelial cells, which are the outermost cells in tissues that make milk (milk) or in the tube from which milk comes out.
  • Breast cancer is known to occur most frequently among women in developed countries, and Korea is the second most common cancer after stomach cancer. In addition, it is the fifth highest mortality cancer after stomach cancer, liver cancer, uterine cancer, and lung cancer.
  • breast cancer In order to reduce mortality from breast cancer, it is important to first diagnose breast cancer early, and secondly, to diagnose the prognosis after treatment by primary surgery and to perform appropriate adjuvant therapy.
  • breast X-ray angiography and ultrasonography are used as preventive screening methods, and this method is most widely used to diagnose early breast cancer.
  • x-ray mammography is a dense breast that is commonly found in Korean women, because of the high fiber content, the diagnosis rate is low, especially the younger women, even if the mammary gland is developed a lot, the diagnosis rate drops.
  • the possibility of developing breast cancer in the diagnosis can not be excluded.
  • ultrasonography is used, but it is also difficult to distinguish between malignant and non-cancer tumors.
  • diagnosis rate is increased by additionally using fine needle aspiration cytology and magnetic resonance imaging.
  • fine needle aspiration cytology and magnetic resonance imaging Even if these methods are used to distinguish between normal and abnormal tissues in a morphological form, it is not easy to distinguish between cancerous and non-cancer tumors.
  • thioredoxin has been found as a coenzyme that donates hydrogen ions to ribonucleotide reductase, an enzyme essential for DNA synthesis of Escherichia coli.
  • Thioredoxin has an active site called -Cys-Gly-Pro-Cys- and is an oxidized form to form disulfide (SS) bond between two cysteine residues and a reduced form to form dithiol (-SH-SH). It is a redox control factor in the cells present.
  • thioredoxin is a small protein on the order of 12 kDa, and includes mammalian thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2).
  • Thioredoxin has many biological activities, for example, (a) thioredoxin acts as a growth factor, (b) removes hydrogen peroxide that is toxic to cells, and (c) thioredoxin in bacteria.
  • NF-kB nuclear transcription factor kB
  • thioredoxin has recently been used as an anti-cancer drug as well as an antioxidant protein drug that protects cells from damage.
  • the present invention provides a method for diagnosing breast cancer comprising measuring thioredoxin 1 from blood.
  • the blood is serum.
  • the method for diagnosing breast cancer by measuring thioredoxin 1 from blood according to the present invention is very easy to collect blood, and thus, unlike conventional breast cancer diagnosis methods for biopsies, it does not burden the patient. Not only can breast cancer be easily diagnosed, but the sensitivity and screening of the diagnosis are high, which can be useful for early diagnosis of breast cancer.
  • 1 is a diagram showing the results of measuring the concentration of thioredoxin 1 using ELISA in the blood of the normal group and breast cancer group.
  • Figure 2 is a diagram showing the results of measuring the concentration of thioredoxin 1 using ELISA in the blood of the breast box patients and other cancer (kidney cancer, lung cancer, colon cancer) patient group.
  • Figure 3 is a diagram showing the results of comparing the concentration of thioredoxin 1 in the blood of the breast cancer and lung cancer patient group.
  • Figure 4 shows the results of measuring the concentration of thioredoxin 1 and other antioxidant proteins TXNDC1 and Grx3 in the blood of the breast cancer patient group.
  • Figure 5 is a diagram showing the results of measuring the concentration of thioredoxin 1 according to the progression of breast and lung cancer.
  • the present invention provides a method for diagnosing breast cancer comprising measuring thioredoxin 1 from blood.
  • the concentration of thioredoxin 1 according to the present invention in the blood of the normal group and the breast cancer patient group was confirmed by ELISA, and thioredoxin 1 was significantly higher in the blood of the breast cancer patient group than the normal group. Indicates concentration.
  • the concentration of thioredoxin 1 in the blood of the breast cancer patient group and other cancer patient groups showed a significantly higher concentration of thioredoxin 1 in the blood of breast cancer patients compared to other cancers.
  • the blood concentration of thioredoxin 1 shows a proportional correlation with the progression of breast cancer.
  • the method for diagnosing breast cancer by measuring thioredoxin 1 from blood according to the present invention is relatively easy to collect blood because it is a sample, unlike the conventional method for diagnosing breast cancer for biopsy. Not only can the diagnosis of breast cancer be very easy, but also the high sensitivity and screening of the diagnosis can be useful for early diagnosis of breast cancer.
  • the ELISA Kit was used for the Express ELISA kit of the US GenScript company for rabbit antibodies, and the antibody for each protein used was purified after Antiserum using a Protein A Column.
  • the concentration of protein in the blood was calculated using a standard curve made using each protein as a standard.
  • the measured value was an average value measured three times, and statistical processing was performed using a statistical program included in GraphPad Prism (ver 5.04) manufactured by GraphPad Software (USA).
  • the concentration of thioredoxin 1 in blood was measured between 50 normal age groups (41 ⁇ 10.39, Mean ⁇ SD) (age distribution: 41-85 years) and 59 breast cancer patients, and the ROC (Receiver operating characteristic) Curve analysis was performed, and the results are shown in FIGS. 1 and 3.
  • the average concentration of thioredoxin 1 in the female normal control (NF) is 28.62 ⁇ 6.054 ng / ml
  • the average concentration in the breast cancer group (BC) is 43.77 As ⁇ 8.182 ng / ml
  • the thioredoxin 1 concentration in the breast cancer group is about 53% higher than the thioredoxin 1 concentration in the normal group.
  • Thioredoxin 1 concentration (BC_D, ductal carcinoma of the breast) was 42.41 ⁇ 8.112 ng / ml
  • lobular breast cancer was about 6.3% higher than coronary breast cancer.
  • thioredoxin 1 is a breast cancer marker for measuring blood that can distinguish about 95% of women from normal women and breast cancer groups, and is a breast cancer marker with excellent sensitivity and selectivity. .
  • thioredoxin 1 was found to be significantly higher only in breast cancer patients among various cancer patients blood as well as female normal control (NF) and male normal control (NM).
  • NF female normal control
  • NM male normal control
  • Table 3 compared with other cancers, it can be seen that the thioredoxin 1 concentration in the blood of breast cancer patients is significantly higher than the concentration in the blood of other cancer patients.
  • the selectivity was found to be 83.0%.
  • Thioredoxin 1 blood concentration data in other cancers lung cancer (LC), kidney cancer (KC), colon cancer (CRC)
  • LC lung cancer
  • KC kidney cancer
  • CRC colon cancer
  • thioredoxin 1 concentration in the blood of breast cancer patients is significantly higher than that in the blood of other cancer patients as well as female and male normal controls (NFM). It can be seen that high.
  • all AUC values Absolute Under Curve values
  • sensitivity and selectivity are about 80% and 60% or more, respectively, and the result shows that thioredoxin 1 is breast cancer. Suggests that it is a specific marker.
  • Thioredoxin Superfamily Thioreedoxin domain-containing protein 1 (TXNDC1) and Grx3 (Glutaredoxin3), which are sensitive to oxidative stress and increase protein synthesis in cells, and thioredoxin 1 breast cancer
  • TXNDC1 Thioredoxin domain-containing protein 1
  • Grx3 Glutaredoxin3
  • TXNDC1 and Grx3 have increased concentrations in the blood of breast cancer patients, but the increase is significantly lower than thioredoxin 1. Furthermore, for TXNDC1 and Grx3, the AUC value is below 0.6 and the blood concentration of thioredoxin 1 shows a statistically significant proportional correlation with the progression of breast cancer. It can be seen that there is no statistically significant correlation with the progress.
  • Lung cancer (LC) group with a large amount of patient blood to re-examine the selectivity of thioredoxin 1 as a breast cancer specific marker and to determine the proportional correlation of blood concentration of thioredoxin 1 according to the progression of breast cancer Comparative analysis was performed and the results are shown in FIG. 5.
  • the lung cancer patient group also shows a similar correlation according to the progression of lung cancer.
  • the increase in thioredoxin 1 in the blood according to cancer progression is attributable to an increase in the blood concentration with an increase in the amount of protein of thioredoxin 1, which in turn increases the oxidative stress as the cancer intensifies. Suggests that. Furthermore, considering that the average thioredoxin 1 blood concentration in the lung cancer patient group is about 35% lower than that in the breast cancer patient group, the increase in breast cancer may be attributed to the specificity of the thioredoxin 1 protein for breast cancer.
  • the method of diagnosing breast cancer by measuring thioredoxin 1 from blood according to the present invention can not only diagnose breast cancer very easily, but also can be usefully used for early diagnosis of breast cancer due to high sensitivity and selectivity of the diagnosis.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Analytical Chemistry (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne une méthode de diagnostic du cancer du sein par le dosage de la thiorédoxine 1 dans le sang. La méthode de diagnostic de l'invention n'est pas contraignante pour la patiente car le dosage est réalisé à partir d'un échantillon de sang qui est relativement facile à collecter, contrairement aux méthodes de diagnostic existantes qui utilisent une biopsie. En outre, la méthode de diagnostic de l'invention permet un diagnostic précoce d'un cancer du sein en raison de sa sensibilité élevée et de sa grande capacité de dépistage.
PCT/KR2011/004729 2009-03-16 2011-06-29 Méthode de diagnostic du cancer du sein Ceased WO2013002433A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/KR2011/004729 WO2013002433A1 (fr) 2011-06-29 2011-06-29 Méthode de diagnostic du cancer du sein
US13/560,208 US9382587B2 (en) 2009-03-16 2012-07-27 Diagnosis of breast cancer based on expression level of thioredoxin-1

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2011/004729 WO2013002433A1 (fr) 2011-06-29 2011-06-29 Méthode de diagnostic du cancer du sein

Related Parent Applications (3)

Application Number Title Priority Date Filing Date
PCT/KR2009/001944 Continuation-In-Part WO2010107158A1 (fr) 2009-03-16 2009-04-15 Marqueur de diagnostic du cancer du sein comprenant de la thiérodoxine-1 comme ingrédient actif et trousse de diagnostic du cancer du sein utilisant ledit marqueur
US13/257,277 Continuation-In-Part US20120003660A1 (en) 2009-03-16 2009-04-15 Diagnosis or prognosis of breast cancer based on expression level of thioredoxin-1
US201113257277A Continuation-In-Part 2009-03-16 2011-09-16

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/560,208 Continuation-In-Part US9382587B2 (en) 2009-03-16 2012-07-27 Diagnosis of breast cancer based on expression level of thioredoxin-1

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WO2013002433A1 true WO2013002433A1 (fr) 2013-01-03

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070105142A1 (en) * 2005-10-31 2007-05-10 Scott Wilhelm Methods for prognosis and monitoring cancer therapy
US20090035801A1 (en) * 2005-12-27 2009-02-05 Power3 Medical Products, Inc. Twelve (12) protein biomarkers for diagnosis and early detection of breast cancer
EP2028492A1 (fr) * 2006-06-05 2009-02-25 Shimadzu Corporation Marqueur tumoral et méthode pour la détermination de l'apparition d'une maladie cancéreuse
KR20100104110A (ko) * 2009-03-16 2010-09-29 배재대학교 산학협력단 티오레독신 1을 유효성분으로 하는 유방암 진단용 마커, 및이를 이용한 유방암 진단 키트

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070105142A1 (en) * 2005-10-31 2007-05-10 Scott Wilhelm Methods for prognosis and monitoring cancer therapy
US20090035801A1 (en) * 2005-12-27 2009-02-05 Power3 Medical Products, Inc. Twelve (12) protein biomarkers for diagnosis and early detection of breast cancer
EP2028492A1 (fr) * 2006-06-05 2009-02-25 Shimadzu Corporation Marqueur tumoral et méthode pour la détermination de l'apparition d'une maladie cancéreuse
KR20100104110A (ko) * 2009-03-16 2010-09-29 배재대학교 산학협력단 티오레독신 1을 유효성분으로 하는 유방암 진단용 마커, 및이를 이용한 유방암 진단 키트

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
IMAI K. ET AL.: "A proteomics study on human breast cancer cell lines by fluorogenic derivatization-liquid chromatography/tandem mass spectrometry.", BIOMEDICAL CHROMATOGRAPHY., vol. 22, 2008, pages 1304 - 14 *

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