2005 Fiscal Year Final Research Report Summary
Development of an anti-cancer agent sensitivity gene diagnosis kit of colorectal cancer with Large-scale quantitative RT-PCR
| Project/Area Number |
16591335
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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 |
Digestive surgery
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| Research Institution | Yokohama City University |
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Principal Investigator |
TOGO Shinji Yokohama City University, Graduate School of Medicine, Department of Gastroenterological Surgery, associate professor, 医学研究科, 準教授 (10244477)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKAWA Yasushi Yokohama City University, Graduate School of Medicine, Department of Gastroenterological Surgery, associate professor, 医学研究科, 準教授 (70254208)
MOMIYAMA Yoshinobu Yokohama City University, Graduate School of Medicine, Department of Gastroenterological Surgery, assistant, 医学研究科, 助手 (20363822)
HAYASHIZAKI Yoshihide RIKEN Genomic Sciences Center, Laboratory for Genome Expression Research Group, project director, ゲノム科学総合研究センター, プロジェクトディレクター (70192705)
SUZUKI Harukazu RIKEN Genomic Sciences Center, Laboratory for Genome Expression Research Group, ゲノム科学総合研究センター, チームリーダー (80333293)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Colorectal cancer / Liver Metastasis / 5FU / Chemosensitivity / OPRT / NAG-1 / TNFRSF1B / SLC35F5 |
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| Research Abstract |
PURPOSE : The aim of this study is to identify genes related to 5-FU sensitivity for colorectal cancer and to apply these genes in prediction of 5-FU sensitivity for liver metastases. METHODS : 81 candidate genes concerning to 5-FU resistance in gastric and colon cancer cell lines had been already reported using a cDNA microarray. In this study, mRNA expression of this 81 selected genes and 5-FU-related enzymes' genes, including thymidylate synthase (TS), dihydropyrimidine dyhydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT) are measured by real-time quantitative RT-PCR assays in surgically resected materials of primary colorectal tumors from 22 patients. Clinical responces were estimated by the effects of 5-FU based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. RESULTS : Four genes (TNFRSF1B, SLC35F5,NAG-1,and OPRT) showed significantly different expression between 5-FU-nonresponding and responding tumors (p<0.05). On that basis, "Response Index" system using three-genes (TNFRSF1B, SLC35F5, and OPRT) was developed by the discriminate analysis that was correlated well with individual chemosensitivity. Among the 11 cases with positive scores by our response-index, 9 achieved reduction of liver metastasis after 5-FU based chemotherapy, whereas the only 1 of the 11 cases with negative scores responded well to chemotherapy, suggesting accuracy rate of 86.3% (p=0.0019). CONCLUSIONS : Our "Response Index" system, consists of TNFRSF1B, SLC35F5, and OPRT, have great potential for predicting the efficacy of 5-FU based chemotherapy for fiver metastasis from colorectal cancer.
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