The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

被引:470
作者
Mascaux, C
Iannino, N
Martin, B
Paesmans, M
Berghmans, T
Dusart, M
Haller, A
Lothaire, P
Meert, AP
Noel, S
Lafitte, JJ
Sculier, JP
机构
[1] Free Univ Brussels, Inst Jules Bordet, Ctr Tumeurs, Dept Intens Care & Thorac Oncol, B-1000 Brussels, Belgium
[2] Free Univ Brussels, Inst Jules Bordet, Ctr Tumeurs, Ctr Data, B-1000 Brussels, Belgium
[3] Free Univ Brussels, Inst Jules Bordet, Ctr Tumeurs, Dept Nucl Med, B-1000 Brussels, Belgium
[4] Free Univ Brussels, Inst Jules Bordet, Ctr Tumeurs, Dept Pathol, B-1000 Brussels, Belgium
[5] CHU Calmette, Chest Dept, Lille, France
[6] FNRS, Brussels, Belgium
[7] Free Univ Brussels, Inst Jules Bordet, Ctr Tumeurs, Dept Surg, B-1000 Brussels, Belgium
关键词
RAS; p21; lung cancer; meta-analysis; systematic review; survival; prognostic factor;
D O I
10.1038/sj.bjc.6602258
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16 - 1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas ( ADC) ( HR 1.59; 95% CI 1.26 - 2.02) and in studies using PCR ( HR 1.40; 95% CI 1.18 - 1.65) but not in studies using IHC ( HR 1.08; 95% CI 0.86 - 1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.
引用
收藏
页码:131 / 139
页数:9
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