Clinical significance of the expression levels of ERCC1, BRCA1 and TS in advanced colorectal cancer

Abstract

Objective To explore the relationship between the expression levels of excision repair cross complementation group 1(ERCC1), breast cancer susceptibility gene 1(BRCA1), thymidylate synthase (TS) mRNA and clinicopathological features, prognosis in advanced colorectal cancer, and the correlation between the expression levels of ERCC1 and BRCA1. Methods The expression levels of ERCC1, BRCA1 and TS mRNA of postoperative paraffin embedded tissue were tested by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in 49 advanced colorectal cancer cases. The results were analyzed by χ2 test of the correlation between the expression levels and clinicopathological characteristics. Patients were followed up by clinic or telephone. The prognosis was analyzed by small sample Kaplan-Meier survival analysis and Log-rank time series analysis, and P<0.05 was statistically significant. Results The expression level of ERCC1 mRNA in patients with colorectal carcinoma had no obvious correlation with the clinical and pathological characteristics such as gender, age, tumor location, lymph node metastasis, distant metastasis, CEA and differentiation degree(P>0.05). The expression level of BRCA1 mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.030) and differentiation degree (P=0.002). The expression level of TS mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.003). The expression level of ERCC1 and BRCA1 mRNA obviously correlated (P=0.002). The 1 year overall survival rate was 95.92% (47/49); the 2 year overall survival rate was 83.67% (41/49); and the 3 year overall survival rate was 73.47% (36/49). Overall survival and progression-free survival time in ERCC1 mRNA low expression group (47.8, 41.0 months) was higher than that in ERCC1 mRNA low expression group (27.3, 20.0 months) respectively (P=0.001, P=0.001). Overall survival and progression-free survival time in BRCA1 mRNA low expression group (43.7, 42.7 months) was higher than that in BRCA1 mRNA high expression group (29.3, 25.1 months) respectively (P=0.009, 0.006). Overall survival time in TS mRNA low expression group (39.8 months) was higher than that in BRCA1 mRNA high expression group (25.2 months). Conclusions The expression level of ERCC1 mRNA is not correlated with its clinical and pathological characteristics, but with its biological characteristics. BRCA1 and TS levels are correlated with invasion and metastasis. Low levels of ERCC1 and BRCA1 expression have a better prognostic effect on platinum based first-line chemotherapy for advanced colorectal cancer, and they are correlated. Low level of TS also has longer disease-free survival. Three joint detection could be used as a prognostic factor for colorectal cancer chemotherapy. Key words: Colorectal cancer; Excision repair cross complementation group 1; Breast cancer susceptibility gene 1; Thymidylate synthase