P16INK4a 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.

Keywords: Aberrant methylation; P16INK4a gene; bronchoalveolar fluid; meta-analysis; serum.