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Abstract
BackgroundThe prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue.MethodsWe searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of p16 hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model.ResultsThe analysis indicated that p16 hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36–2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27–2.55). Moreover, the significant correlation was present between p16 hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19–3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35–2.39) and CRC (HR 1.96, 1.16–3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21–3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73).Conclusions p16 hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.
Highlights
Despite the recent reduction in incidence and mortality, cancer is still a worldwide health burden and leads to more deaths than heart disease in some regions [1]
11 were excluded because the authors assessed p16 methylation using DNA from other than tumor tissues, 31 excluded because it could not permit the calculation of hazard ratios (HRs) estimate owing to the insufficient data reported in these studies, 4 excluded because the data reported in them were overlapped with other studies, and 14 excluded because the assessment was conducted on blood carcinomas
Many efforts have been made to predict the prognosis of cancer patients posterior to surgical treatment by using the molecular analysis of the primary tumor and regional lymph nodes [3,58– 59]
Summary
Despite the recent reduction in incidence and mortality, cancer is still a worldwide health burden and leads to more deaths than heart disease in some regions [1]. A lot of efforts have been made to investigate the prognostic biomarkers including epigenetic markers in cancers, helping to identify high-risk cancer patients who might need adjuvant treatment after surgery. The impact of p16 hypermethylation on prognosis of patients with cancer has been explored recently, the prognostic value of p16 hypermethylation in different tumor types remains conflicting because heterogeneous results were reported in studies and some of them included a small number of patients. To elucidate this issue, we performed this systematic review and metaanalysis to assess the prognostic significance of p16 hypermethylation in various types of cancer. We performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue
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