| Project/Area Number |
16590587
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Mie University |
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Principal Investigator |
SHIRAKI Katsuya Mie University, Hospital, Lecturer, 医学部附属病院, 講師 (90263003)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Kazumoto Mie University, Hospital, Instructor, 医学部附属病院, 助手 (40345971)
SUGIMOTO Kazushi Mie University, School of Medicine, Adjunct Professor, 医学部, 非常勤講師 (60378370)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Proteomics / Hepatoma / Apoptosis / 肝癌 / プロテオーム |
|---|
| Research Abstract |
Hepatocellular carcinoma (HCC) is one of the most fatal cancers with a high incidence in many countries. Hepatitis C virus (HCV) is the most clearly established risk factor for HCC. HCV carriers proceed to chronic hepatitis (CH), to liver cirrhosis (LC), and to HCC after incubation periods. Molecular biomarkers are biological molecules that are indicators of physiologic state and also of change during a carcinogenesis. Mass spectrometry-based protein/peptide profiling and differentially detected proteins in serum or plasma have been identified as diagnostic biomarkers. However, most of them are from degradation fragments of major plasma proteins and few cellular proteins from cancer cells have been reported. To identify sensitive and accurate diagnostic biomarkers, differential plasma proteome profiling which enable us to detect tiny amount of cancer-cell derived protein/peptide in blood. Here we established comprehensive and sensitive analytical platform using automated multi-dimensio
… More
nal μLC-MALDI-TOF/MS and identified several peptide biomarkers which discriminate liver caner and non-cancer disease. Serum samples were pretreated and separated by two-dimensional HPLC ; strong cation exchange (SCX) for the 1^<st> dimension and reverse phase (RP) for the 2^<nd> dimension. The separated samples were spotted onto three MALDI targets automatically. More than 10,000 fractions were analyzed automatically by MALDI-TOF MS in reflector mode. We identified angiotensin II as a spike in processed serum at 1nM concentration. Huge data of the peptide expression profiles generated from mass spectrometry were analyzed by the differential analysis tools originally developed. Analysis of human serum from liver cancer and non-cancer patients revealed several differentially-expressed proteins that indicate ROC value >0.8. Without re-purification, sequential analysis by MS^n on MALDI-QIT-TOF MS revealed post-translational modification of some biomarkers. We identified and validated nine potential biomarkers specific for liver cancer. These novel biomarkers may improve early detection of liver cancer and lead to correct treatment of liver disease. Less
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