APC gene promoter methylation as a potential biomarker for lung cancer diagnosis: A meta-analysis

Background: The aim of this study was to quantitatively analysis the diagnostic performance of adenomatous polyposis coli (APC) gene promoter methylation in serum or sputum/bronchoalveolar lavage fluid (BLAF) as a biomarker for lung cancer identification through pooling of open published data.

Methods: The relevant electronic MEDLINE, EMBASE, Ovid, web of science and CNKI databases were systematically searched to identify the studies related to APC gene promoter methylation for lung cancer diagnosis. Data of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) were extracted from the publications included in the study. The pooled diagnostic sensitivity, specificity and area under summary receiver operating characteristic (SROC) curve (AUC-SROC) of APC gene promoter methylation were calculated. Publication bias was evaluated by Begg's funnel plot and Egger's line regression test.

Results: Fourteen studies associated with APC gene promoter methylation and lung cancer were identified in the databases and finally included in the meta-analysis. The data was pooled using a random effect model due to significant statistical heterogeneity across the 14 studies (p < 0.05). Using the APC gene promoter methylation as a reference for lung cancer identification, the pooled diagnostic sensitivity and specificity were 0.43 (95% CI: 0.40-0.45), and 0.92 (95% CI: 0.90-0.95), respectively with combined diagnostic positive likelihood ratio (+LR) and negative likelihood ratio (-LR) of 7.15 (95% CI: 3.62-14.12) and 0.63 (95% CI: 0.57-0.71). The pooled diagnostic odds ratio (DOR) and AUC-SROC of APC gene promoter methylation for lung cancer diagnosis were 9.84 (95% CI: 5.77-16.79) and 0.7, respectively. The Begg's funnel plot and Egger's line regression test both indicated statistical publication bias (t = 5.40, p < 0.05).

Conclusions: APC gene promoter methylation in serum or sputum/BLAF is a potential biomarker for lung cancer diagnosis with high specificity. However, due to its low sensitivity, it may not be suitable for lung cancer screening in the general population.