mRNA expression of BRCA1, PIAS1, and PIAS4 and survival after second-line docetaxel in advanced gastric cancer.

Abstract

Breast cancer susceptibility gene 1 (BRCA1) has a central role in chemotherapy-induced DNA damage response. The protein inhibitor of activated STAT (PIAS) family of proteins, PIAS1 and PIAS4, are also necessary for adequate DNA damage repair. To further understand the role of BRCA1 in DNA repair, we examined the mRNA expression of these genes in 133 advanced (stage III-IV) gastric cancer patients using quantitative reverse transcription polymerase chain reaction. All P values were two-sided. The median overall survival was 12.5 months (95% confidence interval [CI] = 9.8 to 13.4 months). Among 59 patients receiving second-line docetaxel, the median overall survival was 25.8 months (95% CI = 9.2 to 42.4 months) for patients with high BRCA1 expression, 19.1 months (95% CI = 3.4 to 34.8 months) for those with intermediate expression, and 9.5 months (95% CI = 8.7 to 10.2 months) for those with low expression (P = .0062). The risk of mortality was higher in patients with low BRCA1 levels compared with high BRCA1 levels (hazard ratio of death = 2.49, 95% CI = 1.03 to 5.97, P = .037). Survival in patients receiving second-line docetaxel-based chemotherapy showed a similar trend with PIAS1 and PIAS4 mRNA expression levels, although the associations for PIAS4 were not statistically significant.