Zhao Tingting, Li Wei, Chen Jinfei, Qin Weisong
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 21000, China.
Department of Gynecology, Zhenjiang Maternity and Childcare Hospital, Zhenjiang, 212000, China.
J Cancer. 2021 Jan 1;12(3):849-859. doi: 10.7150/jca.48120. eCollection 2021.
Platinum-based adjuvant chemotherapy is very common for gastric cancer (GC) patients, but the chemotherapy sensitivity is very heterogeneous. The genomic variants and the gene-gene interactions involved in Fas-mediated apoptosis pathway including Fas (FAS 1377 G > A and 670 A > G), FasL (FASL 844 C > T) and caspase-8 (CASP8 -652 6N ins > del or I > D), may paly vital roles in the response to platinum-based treatment. In our investigation, 662 stage II-III postoperative GC patients were enrolled between 1998 and 2006. 261 patients accepted platinum-based regimens and the remaining 401 were not. The log rank tests, Kaplan Meier plots, Pearson chi-square tests, Student t-tests and Cox regression analyses were performed. For the chemotherapy cohort, FAS 1377 G > A or FAS 670 A > G variants alone was related with inferior survival, and a greater than additive effect was identified when patients simultaneously carrying FAS 1377 GA and FAS 670 GA genotypes. But the poor response was neutralized when patients simultaneously carrying FASL 844 C > T or CASP8 -652 6N ins > del mutations. Our study suggested that FAS 1377 G > A and FAS 670 A > G variants may serve as potential biomarkers to predict the response to platinum-based adjuvant chemotherapy, and the gene-gene interactions involved in Fas-mediated apoptosis pathway may enhance or neutralize the chemosensitivity.
铂类辅助化疗在胃癌（GC）患者中非常常见，但化疗敏感性差异很大。Fas介导的凋亡途径中涉及的基因组变异和基因-基因相互作用，包括Fas（FAS 1377 G>A和670 A>G）、FasL（FASL 844 C>T）和半胱天冬酶-8（CASP8 -652 6N ins>del或I>D），可能在铂类治疗反应中发挥重要作用。在我们的研究中，1998年至2006年间纳入了662例II-III期胃癌术后患者。261例患者接受了铂类方案治疗，其余401例未接受。进行了对数秩检验、Kaplan-Meier曲线分析、Pearson卡方检验、Student t检验和Cox回归分析。对于化疗队列，单独的FAS 1377 G>A或FAS 670 A>G变异与较差的生存率相关，当患者同时携带FAS 1377 GA和FAS 670 GA基因型时，发现有大于相加的效应。但当患者同时携带FASL 844 C>T或CASP8 -652 6N ins>del突变时，不良反应被中和。我们的研究表明，FAS 1377 G>A和FAS 670 A>G变异可能作为预测铂类辅助化疗反应的潜在生物标志物，Fas介导的凋亡途径中涉及的基因-基因相互作用可能增强或中和化疗敏感性。
