Development of an anti-cancer agent sensitivity gene diagnosis kit of colorectal cancer with Large-scale quantitative RT-PCR

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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.