Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Rd., Nanjing, China.
J Natl Cancer Inst. 2011 Oct 19;103(20):1552-6. doi: 10.1093/jnci/djr326. Epub 2011 Aug 23.
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.
乳腺癌易感基因 1 (BRCA1) 在化疗诱导的 DNA 损伤反应中起核心作用。蛋白抑制物激活 STAT（PIAS）家族的蛋白，PIAS1 和 PIAS4，对于充分的 DNA 损伤修复也是必需的。为了进一步了解 BRCA1 在 DNA 修复中的作用，我们使用定量逆转录聚合酶链反应（qRT-PCR）在 133 例晚期（III-IV 期）胃癌患者中检测这些基因的 mRNA 表达。所有 P 值均为双侧。中位总生存期为 12.5 个月（95%置信区间 [CI] = 9.8 至 13.4 个月）。在 59 例接受二线多西紫杉醇治疗的患者中，高 BRCA1 表达患者的中位总生存期为 25.8 个月（95%CI = 9.2 至 42.4 个月），中表达患者为 19.1 个月（95%CI = 3.4 至 34.8 个月），低表达患者为 9.5 个月（95%CI = 8.7 至 10.2 个月）（P =.0062）。与高 BRCA1 水平相比，BRCA1 水平低的患者死亡风险更高（死亡风险比 = 2.49，95%CI = 1.03 至 5.97，P =.037）。接受二线多西紫杉醇为基础的化疗的患者的生存情况与 PIAS1 和 PIAS4 的 mRNA 表达水平显示出相似的趋势，尽管 PIAS4 的关联没有统计学意义。
