The Indirect Efficacy Comparison of DNA Methylation in Sputum for Early Screening and Auxiliary Detection of Lung Cancer: A Meta-Analysis

Abstract

Background: DNA methylation in sputum has been an attractive candidate biomarker for the non-invasive screening and detection of lung cancer. Materials and Methods: Databases including PubMed, Ovid, Cochrane library, Web of Science databases, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang, Vip Databases and Google Scholar were searched to collect the diagnostic trials on aberrant DNA methylation in the screening and detection of lung cancer published until 1 December 2016. Indirect comparison meta-analysis was used to evaluate the diagnostic value of the included candidate genes. Results: The systematic literature search yielded a total of 33 studies including a total of 4801 subjects (2238 patients with lung cancer and 2563 controls) and covering 32 genes. We identified that methylated genes in sputum samples for the early screening and auxiliary detection of lung cancer yielded an overall sensitivity of 0.46 (0.41–0.50) and specificity of 0.83 (0.80–0.86). Combined indirect comparisons identified the superior gene of SOX17 (sensitivity: 0.84, specificity: 0.88), CDO1 (sensitivity: 0.78, specificity: 0.67), ZFP42 (sensitivity: 0.87, specificity: 0.63) and TAC1 (sensitivity: 0.86, specificity: 0.75). Conclusions: The present meta-analysis demonstrates that methylated SOX17, CDO1, ZFP42, TAC1, FAM19A4, FHIT, MGMT, p16, and RASSF1A are potential superior biomarkers for the screening and auxiliary detection of lung cancer.

Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood

“…Previous studies have used either case-control or nested case-control designs to study the association between methylation markers and lung cancer risk. Retrospective case-control studies on this topic are not comparable to our study because they either used a different methodology to measure blood leukocyte methylation (Wang et al 2010), or measured methylation biomarkers in sputum as a classifier for lung cancer risk (Leng et al 2017; Liu et al 2017). Three nested case-control studies previously used pre-diagnostic, peripheral blood samples to examine DNA methylation levels associated with lung cancer risk, while adjusting for smoking using self-reported information (Baglietto et al 2017; Fasanelli et al 2015; Sandanger et al 2018).…”

DNA methylation among firefighters

“…Given the long latency between exposures and the development of cancer, ranging from less than 5 years to greater than 30 depending on the type of cancer, DNA methylation biomarkers have the potential to be used to both identify the cumulative effect of exposures and to identify firefighters at increased risk of disease susceptibility. In addition to its use in helping to predict future disease, DNA methylation could potentially be used to assist in determining cancer diagnosis and prognosis, as has been demonstrated in groups other than firefighters [ 99 – 101 ]. For example, the methylation signature identified can be used as an “epigenetic clock” of firefighting.…”

Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer

“…Thus, methylation abnormalities in CDO1 reflect not only the changes that accumulate with progression but also the degree of malignancy. Aiming at practical applications in which CDO1 methylation may serve as a biomarker, research on lung cancer [ 21 ], gastric cancer [ 22 ], colon cancer [ 23 ], HBV-related HCC [ 15 ], and cholangiocarcinoma [ 24 ] has been conducted.…”