Abstract
DNA methylation has been reported to become a potential powerful tool for cancer detection and diagnosis. However, the possibilities for the application of blood-based gene methylation as a biomarker for non-small cell lung cancer (NSCLC) detection and screening remain unclear. Hence, we performed this meta-analysis to evaluate the value of gene methylation detected in blood samples as a noninvasive biomarker in NSCLC. A total of 28 genes were analyzed from 37 case-control studies. In the genes with more than three studies, we found that the methylation of P16, RASSF1A, APC, RARβ, DAPK, CDH13, and MGMT was significantly associated with risks of NSCLC. The methylation statuses of P16, RASSF1A, APC, RARβ, DAPK, CDH13, and MGMT were not linked to age, gender, smoking behavior, and tumor stage and histology in NSCLC. Therefore, the use of the methylation status of P16, RASSF1A, APC, RARβ, DAPK, CDH13, and MGMT could become a promising and powerful biomarker for the detection and screening of NSCLC in blood in clinical settings. Further large-scale studies with large sample sizes are necessary to confirm our findings in the future.
Highlights
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer which has become the top cause of cancer deaths in the world [1]
In the genes with more than three studies, we found that the methylation of P16, RASSF1A, APC, retinoic acid receptor-β gene (RARβ), DAPK, CDH13, and methylguanineDNA methyltransferase (MGMT) was significantly associated with risks of non-small cell lung cancer (NSCLC)
The results showed that the methylated P16 (OR = 17.28, P < 0.001), RASSF1A (OR = 16.41, P < 0.001), APC (OR = 14.01, P < 0.001), RARβ (OR = 7.94, P < 0.001), DAPK (OR = 30.78, P < 0.001), CDH13 (OR = 12.63, P = 0.001) and MGMT (OR = 15.29, P < 0.001) genes were significantly associated with NSCLC in the blood samples (Figures 2–8)
Summary
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer which has become the top cause of cancer deaths in the world [1]. NSCLC includes adenocarcinoma (AC), squamous cell carcinoma (SCC), large cell carcinoma, and adenosquamous carcinoma [2, 3]. NSCLC is commonly diagnosed by a comprehensive evaluation of symptoms, medical imaging, assessment of the levels of serum tumor biomarkers, and, eventually, cytological examination. Imaging methods, such as chest X-rays and computed tomography (CT), are widely used, but they do not have sufficient sensitivity and specificity to detect the early stages of NSCLC [4]. Many studies suggest that the combined detection of several tumor markers, including CEA, PRO-GRP, NSE, SCC-AG, CYFRA21-1, and CA199, is more effective than their single detection [7, 8]
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