2012年10月25日 讯 /生物谷BIOON/ --近日，一项新的研究发现晚期大肠癌患者，如果他们存在一特定的基因突变，阿司匹林可能延长他们的生命。
基于一个简单的PIK3CA测试结果，医生可以给予或不给予患者阿司匹林。因此，PIK3CA测试有可能将大肠癌患者区分开来。但Ogino警告说：然而，研究结果还有待证实。在开展一个独立的验证研究之前，PIK3CA测试是否可以成为常规临床工作的测试方法还有待研究。这项最新研究发表在New England Journal of Medicine杂志上，Ogino团队收集到的数据涉及到900多名大肠癌患者。
Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival
Xiaoyun Liao, M.D., Ph.D., Paul Lochhead, M.B., Ch.B., Reiko Nishihara, Ph.D., Teppei Morikawa, M.D., Ph.D., Aya Kuchiba, Ph.D., Mai Yamauchi, Ph.D., Yu Imamura, M.D., Ph.D., Zhi Rong Qian, M.D., Ph.D., Yoshifumi Baba, M.D., Ph.D., Kaori Shima, D.D.S., Ph.D., Ruifang Sun, M.B., Katsuhiko Nosho, M.D., Ph.D., Jeffrey A. Meyerhardt, M.D., M.P.H., Edward Giovannucci, M.D., M.P.H., Sc.D., Charles S. Fuchs, M.D., M.P.H., Andrew T. Chan, M.D., M.P.H., and Shuji Ogino, M.D., Ph.D.
Background Regular use of aspirin after a diagnosis of colon cancer has been associated with a superior clinical outcome. Experimental evidence suggests that inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2) (also known as cyclooxygenase-2) by aspirin down-regulates phosphatidylinositol 3-kinase (PI3K) signaling activity. We hypothesized that the effect of aspirin on survival and prognosis in patients with cancers characterized by mutated PIK3CA (the phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit alpha polypeptide gene) might differ from the effect among those with wild-type PIK3CA cancers.
Methods We obtained data on 964 patients with rectal or colon cancer from the Nurses' Health Study and the Health Professionals Follow-up Study, including data on aspirin use after diagnosis and the presence or absence of PIK3CA mutation. We used a Cox proportional-hazards model to compute the multivariate hazard ratio for death. We examined tumor markers, including PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and methylation of long interspersed nucleotide element 1.
Results Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with superior colorectal cancer–specific survival (multivariate hazard ratio for cancer-related death, 0.18; 95% confidence interval [CI], 0.06 to 0.61; P<0.001 by the log-rank test) and overall survival (multivariate hazard ratio for death from any cause, 0.54; 95% CI, 0.31 to 0.94; P=0.01 by the log-rank test). In contrast, among patients with wild-type PIK3CA, regular use of aspirin after diagnosis was not associated with colorectal cancer–specific survival (multivariate hazard ratio, 0.96; 95% CI, 0.69 to 1.32; P=0.76 by the log-rank test; P=0.009 for interaction between aspirin and PIK3CA variables) or overall survival (multivariate hazard ratio, 0.94; 95% CI, 0.75 to 1.17; P=0.96 by the log-rank test; P=0.07 for interaction).
Conclusions Regular use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. The findings from this molecular pathological epidemiology study suggest that the PIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy. (Funded by The National Institutes of Health and others.)