KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC: A meta-analysis of 41 studies.
KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC: A meta-analysis of 41 studies.
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KRAS 突变是 NSCLC 不良预后和治疗结果的弱但有效的预测因子：41 项研究的荟萃分析
DOI：
10.18632/oncotarget.7080
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发表时间：
2016-02-16
期刊：
影响因子：
--
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Pan W;Yang Y;Zhu H;Zhang Y;Zhou R;Sun X
癌基因KRAS突变在非小细胞肺癌（NSCLC）中很常见，但其临床意义仍有争议。评估其预后和预测价值的独立研究通常得出不一致的结论。因此，我们对来自多个数据库的41篇相关出版物进行了荟萃分析，以协调这些有争议的结果，并给出KRAS突变在NSCLC中的总体印象。根据我们的研究结果，KRAS突变与早期切除的NSCLC总生存期（OS）和无病生存期（DFS）较差显著相关（风险比或HR分别为1.56和1.57,95% CI分别为1.39-1.76和1.17-2.09），并且与表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKIs）治疗和化疗的较差结果相关(客观缓解率或ORR的相对风险或RR分别为0.21和0.66,95% CI分别为0.12-0.39和0.54-0.81；晚期NSCLC的无进展生存期（PFS） HR=1.46和1.30,95%CI分别为1.23-1.74和1.14-1.50。当排除EGFR突变患者时，KRAS突变仍与EGFR- tkis的OS和PFS恶化显著相关（HR=1.40和1.35,95% CI分别为1.21-1.61和1.11-1.64）。虽然KRAS突变患者化疗的DFS和PFS较差（HR分别为1.33和1.11,95% CI分别为0.97-1.84和0.95-1.30），对EGFR-TKIs或化疗的应答率较低（RR分别为0.55和0.88,95% CI分别为0.27-1.11和0.76-1.02），但差异无统计学意义。总之，KRAS突变是NSCLC不良预后和治疗结果的一个弱但有效的预测因子。有必要开发针对KRAS突变肺癌和其他肿瘤的靶向治疗方法。
Mutation of oncogene KRAS is common in non-small cell lung cancer (NSCLC), however, its clinical significance is still controversial. Independent studies evaluating its prognostic and predictive value usually drew inconsistent conclusions. Hence, We performed a meta-analysis with 41 relative publications, retrieved from multi-databases, to reconcile these controversial results and to give an overall impression of KRAS mutation in NSCLC. According to our findings, KRAS mutation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in early stage resected NSCLC (hazard ratio or HR=1.56 and 1.57, 95% CI 1.39-1.76 and 1.17-2.09 respectively), and with inferior outcomes of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment and chemotherapy (relative risk or RR=0.21 and 0.66 for objective response rate or ORR, 95% CI 0.12-0.39 and 0.54-0.81 respectively; HR=1.46 and 1.30 for progression-free survival or PFS, 95%CI 1.23-1.74 and 1.14-1.50 respectively) in advanced NSCLC. When EGFR mutant patients were excluded, KRAS mutation was still significantly associated with worse OS and PFS of EGFR-TKIs (HR=1.40 and 1.35, 95 % CI 1.21-1.61 and 1.11-1.64). Although KRAS mutant patients presented worse DFS and PFS of chemotherapy (HR=1.33 and 1.11, 95% CI 0.97-1.84 and 0.95-1.30), and lower response rate to EGFR-TKIs or chemotherapy (RR=0.55 and 0.88, 95 % CI 0.27-1.11 and 0.76-1.02), statistical differences were not met. In conclusion, KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC. There's a need for developing target therapies for KRAS mutant lung cancer and other tumors.