Lung Cancer：K-ras基因突变与NSCLC患者生存率下降相关

20%-30%的非小细胞肺癌（NSCLC）患者存在K-ras基因突变，其中腺癌存在该基因突变者尤为常见。然而，有关K-ras基因突变对非小细胞肺癌患者的预后价值，目前仍没有明确的结论。为了加深对这一问题的了解，来自我国卫生部肺部疾病重点实验室，华中科技大学同济医学院附属协和医院呼吸与危重医学科的辛建宝及其同事进行了一项研究，研究结果发表于2013年4月19日的《肺癌》（Lung Cancer）杂志上。研究结果显示：K-ras基因突变与非小细胞肺癌较差的整体生存率相关，这种相关性在腺癌患者、和早期患者中尤其明显。

该研究是一项针对相关文献的系统回顾与荟萃分析，旨在评估K-ras基因突变对非小细胞肺癌的预后价值。在对发表的相关文献进行了方法学评价之后，研究者对文献中的患者存活数据进行了汇总；并计算出了患者总生存期合并后的风险比（HR）、及相应的95%可信区间（CI）。

该研究的主要结果为：共有41个试验的6939例患者被纳入分析，其总的总生存期HR为1.45，95%CI为1.29-1.62，这表明K-ras基因突变对非小细胞肺癌患者的生存率有不利影响。随后进行的亚组分析显示：在种族方面的亚组分析中，亚洲人总生存期合并后的HR为1.97，95%CI为1.58-2.44；而非亚洲人的这一数值为1.37，95%CI为1.25-1.5。在组织学亚组方面，腺癌患者总生存期合并后的HR为1.39，95%CI为1.24-1.55，这表明K-ras基因突变与腺癌患者的生存期缩短相关。

在根据疾病分期进行的亚组分析中，K-ras基因突变是早期患者的不良预后因素：其中，I期患者总生存期合并后的HR为1.81，95% CI为1.36-2.39；而I-IIIa期患者的这一数据为1.68，95%CI为1.11-2.55；但IIIB~IV期的晚期患者总生存期合并后的HR为1.3；95%CI为0.99-1.71，这说明K-ras基因突变与患者的预后关系，在早、晚期患者中有所不同。最后，在针对测试方法进行的亚组分析中，所有四种K-ras基因突变测试方法的结果，对非小细胞肺癌患者的生存率均有统计学意义的显著影响。其中，PCR-MSOP亚组的HR为1.73，95%CI为1.35-2.2；PCR-DGGE亚组为1.27，95% CI为1.01-1.62；PCR-RFLP亚组为1.88；95%CI 为1.42-2.49；而PCR-seq亚组为1.34，95%CI为1.14-1.58。

该研究结果显示：荟萃分析表明，K-ras基因突变与非小细胞肺癌较差的整体生存率相关，这种相关性在腺癌患者、和早期患者中尤其明显。 

Prognostic value of K-RAS mutations in patients with non-small cell lung cancer: A systematic review with meta-analysis.
Abstract
K-RAS gene mutations have been found in 20-30% of non-small cell lung cancer and occur most commonly in adenocarcinoma, however, there was no definitive conclusion about the prognostic role of K-RAS mutations in NSCLC. Herein we performed a systematic review of the literatures with meta-analysis to assess K-RAS mutations' prognostic value in NSCLC. After a methodological assessment, survival data from published studies were aggregated. Combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. 41 trials (6939 patients) were included in the analysis, the overall HR was 1.45 (95% CI: 1.29-1.62), showing that K-RAS mutations have an unfavorable impact on survival of patients with NSCLC. Then a subgroup analysis was performed about ethnicity, the combined HR was 1.97 (95% CI: 1.58-2.44) for Asians, and 1.37 (95% CI: 1.25-1.5) for non-Asians. In subgroup analysis of histology, the HR was 1.39 (95% CI: 1.24-1.55) for adenocarcinoma, suggesting that K-RAS mutations were correlated with shortened survival for adenocarcinoma. When the subgroup analysis was conducted according to disease stage, K-RAS mutations were poor prognostic factors in early stages: stage I (1.81; 95% CI: 1.36-2.39) and stage I-IIIa (1.68; 95% CI: 1.11-2.55), but not in advanced stage (IIIb-IV) (1.3; 95% CI: 0.99-1.71). At last, in subgroup analysis about test methods, all of the four methods: PCR-MSOP (1.73; 95% CI: 1.35-2.2), PCR-DGGE (1.27; 95% CI: 1.01-1.62), PCR-RFLP (1.88; 95% CI: 1.42-2.49) and PCR-seq (1.34; 95% CI: 1.14-1.58) showed statistically significant impact on survival of NSCLC patients. In conclusion, this meta-analysis suggests that K-RAS mutations are associated with a worse overall survival in patients with NSCLC, especially in patients with adenocarcinoma and early stage.