DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update

Abstract

Lung cancer is the number one cancer killer in the United States. This disease is clinically divided into two sub-types, small cell lung cancer, (10-15% of lung cancer cases), and non-small cell lung cancer (NSCLC; 85-90% of cases). Early detection of NSCLC, which is the more common and less aggressive of the two sub-types, has the highest potential for saving lives. As yet, no routine screening method that enables early detection exists, and this is a key factor in the high mortality rate of this disease. Imaging and cytology-based screening strategies have been employed for early detection, and while some are sensitive, none have been demonstrated to reduce lung cancer mortality. However, mortality might be reduced by developing specific molecular markers that can complement imaging techniques. DNA methylation has emerged as a highly promising biomarker and is being actively studied in multiple cancers. The analysis of DNA methylation-based biomarkers is rapidly advancing, and a large number of potential biomarkers have been identified. Here we present a detailed review of the literature, focusing on DNA methylation-based markers developed using primary NSCLC tissue. Viable markers for clinical diagnosis must be detectable in 'remote media' such as blood, sputum, bronchoalveolar lavage, or even exhaled breath condensate. We discuss progress on their detection in such media and the sensitivity and specificity of the molecular marker panels identified to date. Lastly, we look to future advancements that will be made possible with the interrogation of the epigenome.

Asbestos‐associated genome‐wide DNA methylation changes in lung cancer

“…Epigenetic regulation of these genes has been strongly implicated earlier in lung cancer. [37][38][39][40][41] However, methylation in genes such as CDKN2A did not cross the thresholds in our study possibly because differing methylation patterns in CDKN2A has been reported in different lung cancer histological types. 42 We detected smoking-related methylation changes in several CpGs or genes that have earlier been reported to associate with smoking.…”

Aberrant Methylation of Genes in Sputum Samples as Diagnostic Biomarkers for Non-small Cell Lung Cancer: a Meta-analysis

“…However, none of these methods is truly optimal, either on account of improper sensitivity or specificity of the tests, or the methods are costly and invasive (Melvyn et al, Xu Wang 1 , Li Ling 2 , Hong Su 1 *, Jian Cheng 1 , Liu Jin 1 Paul et al, 2008). Since these options have not been proven effective as early detection methods, sensitive and specific diagnostic methods remains to be found (Parkin et al, 2001).…”

“…The advantages of sputum as "remote media" included its non-invasive procurement, and the fact that it contains cells from the lungs and lower respiratory tract (Olaussen et al, 2005;Paul et al, 2008). Shin et al (2012) described a combination of 2 loci, MAGE A3 and p16 that served as a good panel for early detection of lung cancer in sputum specimen.…”

“…The remaining 85-90% of cases is classified as NSCLC. Early detection of NSCLC, which is the more common and less aggressive sub-type, has the highest potential for saving lives (Paul et al, 2008).…”

Methylation of TMEFF2 Gene in Tissue and Serum DNA from Patients with Non-Small Cell Lung Cancer

“…Moreover, aberrant promoter methylation often occurs as very early events during cancer development (Baylin and Ohm, 2006). To date, a number of genes can now be methylated in lung cancer, which shows great promise for early detection of lung cancer (Anglim et al, 2008;Belinsky, 2004;Heller et al, 2010;Lee et al, 2011).…”