Abstract
BackgroundThe prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC.MethodsRelevant studies were identified by searching PubMed, Embase and Web of Science databases until June 2012. The association of p16 methylation with both overall survival (OS) and disease-free survival (DFS) was preformed. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses, sensitivity analysis and publication bias were also conducted.ResultsA total of 18 studies containing 2432 patients met the inclusion criteria and had sufficient survival data for quantitative aggregation. The results showed that p16 methylation was an indicator of poor prognosis in NSCLC. The HR was 1.36 (95% CI: 1.08–1.73, I2 = 56.7%) and 1.68 (95% CI: 1.12–2.52, I2 = 38.7%) for OS and DFS, respectively. Subgroup analyses were carried out. The HRs of fresh and paraffin tissue were 1.50 (95% CI: 1.11–2.01) and 1.10 (95% CI: 0.77–1.57). The pooled HR was 1.40 (95% CI: 1.02–1.92) for methylation-specific PCR (MSP) and 1.26 (95% CI: 0.87–1.82) for quantitative MSP (Q-MSP). The combined HR of the 16 studies reporting NSCLC as a whole indicated that patients with p16 hypermethylation had poor prognosis. No significant association was found when adenocarcinoma subtype pooled. When seven studies on DFS were aggregated, the HR was 1.68 (95% CI: 1.12–2.52) without significant heterogeneity. Moreover, no obvious publication bias was detected on both OS and DFS.ConclusionThe meta-analysis findings support the hypothesis that p16 methylation is associated with OS and DFS in NSCLC patients. Large well-designed prospective studies are now needed to confirm the clinical utility of p16 methylation as an independent prognostic marker.
Highlights
With more than 1.6 million cases diagnosed annually, lung cancer is the leading cause of cancer-related deaths in men and the second leading cause of cancer deaths in women worldwide [1]
Selection and Characteristics of Studies By the initial literature search, 145 records were identified regarding the association of p16 methylation status and non-small cell lung cancer (NSCLC) survival; 111 studies were excluded after screening the titles or abstracts because they were either review articles, abstracts, no on human being, duplicate publication, or studies irrelevant to the current theme
Seventeen studies dealt with NSCLC of all histological subtypes, one with adenocarcinoma only [32]
Summary
With more than 1.6 million cases diagnosed annually, lung cancer is the leading cause of cancer-related deaths in men and the second leading cause of cancer deaths in women worldwide [1]. There is increasing evidence that epigenetic alterations, inactivation of tumor suppressor genes or tumor-related genes through promoter hypermethylation, play a dominant role in various cancers including lung cancer [2,3]. Promoter CpG island methylation is the most widely studied and best characterized epigenetic alteration in NSCLC, providing some of the most promising markers for early detection and prediction of prognosis or treatment response in NSCLC (see review article [4]). The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC
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