Predicting 5-fluorouracil chemosensitivity of liver metastases from colorectal cancer using primary tumor specimens: Three-gene expression model predicts clinical response
✍ Scribed by Ryusei Matsuyama; Shinji Togo; Daisuke Shimizu; Nobuyoshi Momiyama; Takashi Ishikawa; Yasushi Ichikawa; Itaru Endo; Chikara Kunisaki; Harukazu Suzuki; Yoshihide Hayasizaki; Hiroshi Shimada
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 131 KB
- Volume
- 119
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
We identified genes related to 5‐fluorouracil (5‐FU) sensitivity in colorectal cancer and utilized these genes for predicting the 5‐FU sensitivity of liver metastases. Eighty‐one candidate genes involved in 5‐FU resistance in gastric and colon cancer cell lines were previously identified using a cDNA microarray. In this study, the mRNA expression levels of these 81 selected genes and the genes of 5‐FU‐related enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real‐time quantitative RT‐PCR assays of surgically resected materials from primary colorectal tumors in 22 patients. Clinical responses were estimated by evaluating the effects of 5‐FU‐based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. Four genes (TNFRSF1B, SLC35F5, NAG‐1 and OPRT) had significantly different expression profiles in 5‐FU‐nonresponding and responding tumors (p < 0.05). A “Response Index” system using three genes (TNFRSF1B, SLC35F5 and OPRT) was then developed using a discriminate analysis; the results were well correlated with the individual chemosensitivities. Among the 11 cases with positive scores in our response index, 9 achieved a reduction in their liver metastases after 5‐FU‐based chemotherapy, whereas only 1 of the 11 cases with negative scores responded well to chemotherapy. Our “Response Index” system, consisting of TNFRSF1B, SLC35F5 and OPRT, has great potential for predicting the efficacy of 5‐FU‐based chemotherapy against liver metastases from colorectal cancer. © 2006 Wiley‐Liss, Inc.