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

Abstract

BackgroundThis 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).MethodsTwo 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.ResultsTwenty‐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.

Distal‐type bronchiolar adenoma of the lung expressing p16INK4a – morphologic, immunohistochemical, ultrastructural and genomic analysis – report of a case and review of the literature

“…The gene promotor methylation of tumor suppressor p16 INK4a (often simply referred to p16) has also been detected in non‐small cell lung carcinoma (NSCLC), leading to loss of expression of p16 INK4a protein 11 . Together with the key tumor suppressors P14ARF and P15INK4b, p16 INK4a is encoded by the INK4/ARF locus, one of the most affected genomic regions in human cancer cells 11,12 . Zhou et al 12 .…”

“…The gene promotor methylation of tumor suppressor p16 INK4a (often simply referred to p16) has also been detected in non-small cell lung carcinoma (NSCLC), leading to loss of expression of p16 INK4a protein. 11 BRAF V600E mutation is frequently found in various benign tumors. Most melanocytic nevi and a subset of colonic serrated polyps/adenomas show the mutation.…”

Promoter Methylation of Selected Genes in Non-Small-Cell Lung Cancer Patients and Cell Lines

“…The genes CDH1, CDKN2Ap16, RASSF1A, TERT , and WT1 were selected based on their roles as biomarkers in NSCLC and their putative gender sensitivity based on the current literature and our own research findings (reviewed in [ 64 ]). Among the selected markers, RASSF1A [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ] and, to a lesser extent, CDKN2Ap16 [ 73 , 74 , 75 , 76 , 77 ] are already accepted as methylation markers. The applicability of CDH1 [ 78 , 79 , 80 , 81 , 82 , 83 ] and WT1 [ 45 , 61 , 84 , 85 ] is still under investigation but may have a broader impact on many cancer entities; their interdependence adds to this potential.…”

From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

“…Bronchoalveolar lavage (BAL) is a non-invasive procedure useful for diagnostic purposes in different lung diseases. 100 Tuo et al 101 identified the potential role of P16INK4a gene promoter methylation in both BAL and sputum as a diagnostic biomarker for NSCLC, but because of the low sensitivity, it is not suitable as a screening tool. Ren et al 102 showed that SHOX2 and RASSF1A methylation in BAL can increment the detection rate of lung cancer, with high sensitivity and specificity.…”