Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen.
Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden.
Ann Oncol. 2013 Oct;24(10):2581-2588. doi: 10.1093/annonc/mdt330. Epub 2013 Aug 23.
To determine the prognostic role of selected microRNA (miRNA) polymorphisms in advanced gastric cancer (AGC).
Six hundred and seventy-four AGC patients received 5-fluorouracil (F), leucovorin (L), oxaliplatin (O) or FL + cisplatin (P) or additional docetaxel (T) to FLO (FLOT) within four clinical trials. Polymorphisms of mir-26a1 (rs7372209), mir-27a (rs895819), mir-100 (rs1834306), mir-146a (rs2910164), mir-196-a2 (rs11614913), mir-219-1 (rs107822) and mir-423 (rs6505162) were genotyped. Variable selection for the final multivariate model (n = 487) was based on univariate and multivariate Cox-regression analyses with a cut-off P-value of ≤ 20%.
Genetic factors significantly associated with overall survival (OS) were rs7372209 (mir-26a1) variant genotypes (hazard ratio, HR 1.307 [95% confidence interval (CI) 1.031-1.656], P = 0.0272), rs895819 (mir-27a) variant genotypes (HR 1.304 [95% CI 1.031-1.650], P = 0.0270) and rs11614913 (mir-196a2) variant genotypes (HR 0.791 [95% CI 0.625-1.000], P = 0.0497). Clinical factors with significant impact on OS were Eastern Cooperative Oncology Group (ECOG) 2 performance status (HR 1.880 [95% CI 1.254-2.820], P = 0.0023), curative surgery of advanced disease (HR 0.235 [95% CI 0.123-0.449], P < 0.0001) and addition of docetaxel in locally AGC patients (HR 0.348 [95% CI 0.145-0.838], P = 0.0301). Combined analyses revealed an improved OS in patients without any unfavourable genotype of 18 months compared with 14, 12 and 10 months in patients with 1, 2 and 3 unfavourable genotypes, respectively (P = 0.0257).
These data suggest a significant impact of selected miRNA polymorphisms on prognosis in AGC.
为了确定选定的 microRNA (miRNA) 多态性在晚期胃癌 (AGC) 中的预后作用。
674 名 AGC 患者在四项临床试验中接受了 5-氟尿嘧啶 (F)、亚叶酸 (L)、奥沙利铂 (O) 或 FL + 顺铂 (P) 或额外的多西他赛 (T) 治疗 FLO (FLOT)。对 mir-26a1(rs7372209)、mir-27a(rs895819)、mir-100(rs1834306)、mir-146a(rs2910164)、mir-196-a2(rs11614913)、mir-219-1(rs107822)和 mir-423(rs6505162)的多态性进行了基因分型。最终多变量模型 (n = 487) 的变量选择基于单变量和多变量 Cox 回归分析，截断 P 值≤20%。
与总生存期 (OS) 显著相关的遗传因素是 rs7372209(mir-26a1)变体基因型 (危险比, HR 1.307[95%置信区间 (CI) 1.031-1.656], P = 0.0272)、rs895819(mir-27a)变体基因型 (HR 1.304[95%CI 1.031-1.650], P = 0.0270) 和 rs11614913(mir-196a2)变体基因型 (HR 0.791[95%CI 0.625-1.000], P = 0.0497)。对 OS 有显著影响的临床因素是东部肿瘤协作组 (ECOG) 2 表现状态 (HR 1.880[95%CI 1.254-2.820], P = 0.0023)、晚期疾病的根治性手术 (HR 0.235[95%CI 0.123-0.449], P<0.0001) 和局部 AGC 患者中多西他赛的添加 (HR 0.348[95%CI 0.145-0.838], P = 0.0301)。联合分析显示，与具有 1、2 和 3 种不利基因型的患者相比，无任何不利基因型的患者的 OS 得到改善，18 个月的 OS 为 14、12 和 10 个月 (P = 0.0257)。
这些数据表明，选定的 miRNA 多态性对 AGC 的预后有显著影响。
