RTSβ as a Novel 5-fluorouracil Resistance Marker of Colorectal Cancer: A Preliminary Study

Abstract

Introduction: Colorectal cancer is the most common form of malignancy in Taiwan and the third leading cause of death from cancer, preceded only by lung and hepatic cancers. Colorectal cancer is typically treated by surgical intervention and/or chemotherapy and radiotherapy, if necessary. To date, 5-fluorouracil (5-FU) is the most commonly used anti-cancer chemotherapy drug. However, patients commonly experience resistance to the drug therefore limiting its efficiency. In this study, we measured the expression of rTSβ in human colon cancer as a novel 5-FU resistance marker. Materials and Methods: We collected 172 colon cancer samples from 4 different hospitals (including 21 pairs of colon cancer biopsies and 151 pathologic slides of colon cancer). In vitro, we measured the cytotoxicity of 5-FU and 5-FU plus leucovorin in H630 and H630-1 colon cancer cell lines. Results: The results revealed that rTSβ was expressed in 115 (66.9 %) pathology samples and that tumour expression was higher than in corresponding normal tissue. Survival rates of up to 5 years following treatment was significantly higher for patients without rTSβ expression than for those with rTSβ expression (P = 0.0023). In vitro, H630-1 (with rTSβ overexpression) had significantly higher IC50 of 5-FU than did H630. IC50of 5-FU decreased when leucovorin was added. Conclusions: Results indicate a close relationship between rTSβ expression and resistance to the drug 5-FU in human colorectal cancer. These results provide further evidence for rTSβ expression as a novel 5-FU resistance marker of colorectal cancer. Key words: Chemotherapy, Immunohistochemistry, Prognosis