P16 INK4a gene promoter methylation as a biomarker for the diagnosis of non-small cell lung cancer: An updated meta-analysis

Abstract

Background: This meta-analysis was conducted to investigate the diagnostic performance of P16 INK4a gene promoter methylation as a biomarker of non-small cell lung cancer (NSCLC). Methods: Two reviewers independently searched the Web of Science, PubMed, Cochrane, Embase, China National Knowledge Infrastructure, and Chinese Biomedical Literature databases. Publications relevant to P16 INK4a gene promoter methylation in serum or bronchoalveolar fluid/sputum were screened and included in this meta-analysis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated. Results: Twenty-six publications with 1768 lung cancer cases and 1323 controls were included. The pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were 0.46 (95% confidence interval [CI] 0.43–0.48), 0.90 (95% CI 0.88–0.91), 6.33 (95% CI 3.89–10.30), 0.57 (95% CI 0.50–0.65) and 10.72 (95% CI 6.94–16.56), respectively, for P16 INK4a gene promoter methylation as a biomarker for the diagnosis of NSCLC. The area under the symmetric receiver operating characteristic curve was 0.75 with a standard error of 0.004. No publication bias was detected via line regression test (t = 0.95; P = 0.35) and Begg's funnel plot. Conclusion: P16 INK4a gene promoter methylation detection in serum or bronchoalveolar fluid/sputum may be a potential biomarker for NSCLC diagnosis; however, the sensitivity was relatively low, which is not suitable for NSCLC screening.