| Project/Area Number |
16390353
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Chiba University |
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Principal Investigator |
TOMONAGA Takeshi Chiba University, Graduate School of Medicine, Department of Molecular Diagnosis, Associate Prof., 大学院・医学研究院, 助教授 (80227644)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Hideaki Chiba University, Graduate School of Medicine, Department of Frontier Surgery, Assistant Prof., 大学院・医学研究院, 講師 (20292691)
MATSUSHITA Kazuyuki Chiba University, Graduate School of Medicine, Department of Frontier Surgery, Assistant Prof., 大学院・医学研究院, 助手 (90344994)
NOMURA Fumio Chiba University, Graduate School of Medicine, Department of Molecular Diagnosis, Professor, 大学院・医学研究院, 教授 (80164739)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥10,400,000 (Direct Cost: ¥10,400,000)
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| Keywords | proteomics / gastrointestinal cancer / early diagnosis / tumor marker / two differential electrophoresis / 2D-DIGE / SELDI TOF-MS / 固形癌 / プロテインチップシステム / 分子標的治療 |
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| Research Abstract |
Cancer has been the disease with the highest cause of death for a decade. This is partly due to the lack of ideal tumor markers for early diagnosis. Therefore, development of tumor markers with higher sensitivity and specificity is waiting to emerge. Recent advances in proteomic technology made it possible to identify novel tumor markers for various cancers. There are two prominent types of proteomic approaches, 2D gel-based (2DE) and MS/MS based approach.
In this study, we identified 36 proteins whose expression is altered in primary colorectal cancer by 2-DE. The overexpression of several proteins in tumors was confirmed by Western blotting. Among them, the expression of eukaryotic translation initiation factor 41-1 (eIF-4H) isoform 1 greatly increased in most of the tumor tissues. Moreover, post-translational modifications of the prolyl-4-hydroxylase β subunit (P4HB), annexin A2, and triosephosphate isomerase 1 (TPI1) were also identified. We also identified 33 proteins with altered
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expression between cancer and adjacent non-cancer tissues in primary esophageal cancer using fluorescent 2D differential gel electrophoresis (2D-DIGE). A 195kDa protein. periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and scarcely expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression.
On the other hand, surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to find novel serum biomarkers for pancreatic cancer. Protein profiling analysis identified clusters of 85 peaks, which were differentially expressed in the pre- and postoperative sera of pancreatic cancer patients. Among these peaks, the peak intensity levels of 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum of 20 patients (P<0.002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1) and its truncated form. The high level of ApoC-1 in preoperative serum was significantly correlated with a poor prognosis. These data strongly suggest that the serum ApoC-1 level is a useful prognostic marker in pancreatic cancer patients. Less
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