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Review
, 92 (1), 131-9

The Role of RAS Oncogene in Survival of Patients With Lung Cancer: A Systematic Review of the Literature With Meta-Analysis

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Review

The Role of RAS Oncogene in Survival of Patients With Lung Cancer: A Systematic Review of the Literature With Meta-Analysis

C Mascaux et al. Br J Cancer.

Abstract

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.

Figures

Figure 1
Figure 1
Meta-analysis of studies assessing RAS with IHC in NSCLC. Hazard ratio (HR) and 95% confidence interval (CI) of survival in studies evaluating RAS-p21 status in NSCLC. HR>1 implies a survival disadvantage for the group with p21 expression. The square size is proportional to the number of patients included in the study. The center of the lozenge gives the combined HR of the meta-analysis and its extremities the 95% confidence interval. HR=1.08; CI 95% 0.86–1.34. Total number of patients: 989.
Figure 2
Figure 2
Meta-analysis of studies assessing RAS mutation with PCR in NSCLC. Hazard ratio (HR) and 95% confidence interval (CI) of survival in studies evaluating RAS-p21 status in NSCLC. HR>1 implies a survival disadvantage for the group with RAS mutation. The square size is proportional to the number of patients included in the study. The centre of the lozenge gives the combined HR of the meta-analysis and its extremities the 95% confidence interval. HR=1.40; CI 95% 1.18–1.65. Total number of patients: 2631.
Figure 3
Figure 3
Meta-analysis of studies assessing RAS mutation by PCR in adenocarcinomas. Hazard ratio (HR) and 95% confidence interval (CI) of survival in studies evaluating RAS-p21 status in NSCLC. HR>1 implies a survival disadvantage for the group with RAS mutation. The square size is proportional to the number of patients included in the study. The centre of the lozenge gives the combined HR of the meta-analysis and its extremities the 95% confidence interval. HR=1.50; CI 95% 1.26–1.80. Total number of patients: 1170.

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