Can P16 Methylation Profiling of Cancer Tissues Predict the Clinical Outcome of Patients with Non-Small Cell Lung Cancer After? a Systematic Review and Meta-Analysis

Abstract

ABSTRACT Aim: p16 methylation profiling of cancer tissues has identified as an important component of carcinogenesis in non-small cell lung cancer (NSCLC). But whether or not p16 promoter hypermethylation has any prognostic value on the survival of patients with NSCLC is uncertain.We performed a systematic review and meta-analysis to investigate the prognostic value of p16 promoter methylation and its prognostic implication in non-small cell lung cancer patients. Methods: All data that were associated with the study of the relationship between p16 methylation and the prognosis in non-small cell lung cancer was searched from Cochrane library, PubMed, Embase and Medline database. We extracted hazard ratios (HRs) and associated 95% confidence intervals (CIs) from the identified studies, the random or fixed effect model was applied to estimate the pooled data based on the heterogeneity analysis. Data pooling was performed by RevMan 4.2. Results: 20 studies containing 2514 patients were included in this Meta-analysis. The results indicated that p16 hypermethylation had significant association with poor OS (HR 1.56, 95% CI: 1.20-2.04) and short disease-free survival (DFS) (HR 2.17, 95% CI 1.39-3.40) in non-small cell lung cancer (NSCLC). The studies were categorized according to histology, disease stage and laboratory technique. The adenocarcinoma subgroup had an HR of 2.11 [95% CI 1.65-2.75] with statistical significance. In early stage NSCLC (I-II), the aggregated HR was 2.65 [95% CI: 1.88-3.73], showing a worse survival for NSCLC with p16 hypermethylation. Both results were insignificant with the HR of 1.39 [95% CI: 0.99-1.94] and 1.81 [95% CI: 0.71-4.58] detecting p16 methylation by methylation-specific PCR and qualitatively analyze.The HRs of fresh and paraffin tissue were 1.64 (95% CI: 1.09–2.46) and 1.40 (95% CI: 0.89–2.22). Moreover, no obvious publication bias was detected on both OS and DFS. Conclusions: Tumor tissue p16 promoter methylation appears to be an independent negative prognostic factor to overall survival and disease-free survival of non-small cell lung cancer patients, and also show poor prognostic value in subset of lung adenocarcinoma and the early stage of non-small cell lung cancer (I-II). Additional studies with large patient number and widely accepted practical methods are required to derive the more precise outcome. Disclosure: All authors have declared no conflicts of interest.