Lung Cancer Epigenetics: Emerging Biomarkers

Abstract

Executive summary DNA methylation as a tumor biomarkerEpigenetic abnormalities are present in all human cancers and are currently considered to be the hallmark of cancer initiation and progression. Currently, the best-studied epigenetic event in the mammalian genome is DNA methylation, which is a chemical covalent modification of cytosine. The virtually universal presence of DNA hypermethylation in all types of cancer makes it an ideal candidate tumor biomarker. DNA methylation is chemically stable, it can be readily amplifiable and is easy to detect. In lung cancer, aberrant DNA methylation can be detected in tissues, in plasma/serum, in sputum, in bronchial lavage and saliva.Circulating tumor DNA Cell-free DNA maintains the genetic and epigenetic profile of its primary tumor source. A plethora of loci have been reported to be methylated in the plasma/serum of non-small-cell lung cancer (NSCLC) patients, suggesting novel potential diagnostic and prognostic targets such as APC, CDH1, MGMT, DCC, RASSF1A and others. DNA methylation as a tumor biomarker in lung cancerA variety of epigenetic biomarkers have been evaluated so far in lung cancer diagnostics. The diagnostic value of RASSF1A methylation and KRAS mutations in bronchial washings reported a 29% efficiency of detecting malignancy in false-negative or ambiguous cytology outcomes. SHOX2 quantified methylation showed promising results in bronchial aspirates, with a sensitivity of 78% and a specificity of 96% while SHOX2 sensitivity and specificity in plasma was 60 and 90%, respectively. Promoter methylation of APC, RASSF1A, p16 and CDH13 associated with early recurrence in stage 1 NSCLC. Promoter methylation of BRMS1 correlates with smoking history and poor survival in NSCLC.

CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

“…Despite the tremendous mountainous progress in multidisciplinary therapy, the overall 5-year survival rate is still poor [3]. One of the major obstacles restricting therapeutic efficiency is intrinsic or acquired resistance to chemotherapeutic agents in clinical practice [4-8].…”

Effect of DR4 promoter methylation on the TRAIL-induced apoptosis in lung squamous carcinoma cell

“…An abnormally high expression can directly or indirectly block gene transcription, resulting in silencing or a function of the cell cycle regulatory gene, DNA repair gene, apoptosis gene, tumor suppressor gene and other related genes, which may be one of the main factors inducing tumors (29,30). In lung carcinoma and other carcinoma cells, the abnormal increase in the methylation levels of some gene CpG island regions is their main characteristic (31). For colorectal cancer, previous findings have shown an abnormal methylation is a characteristic factor in the regulation of CPT-11 metabolic enzyme change.…”

Epigenetics in lung cancer diagnosis and therapy

“…Unfortunately, the mortality rate closely parallels the incidence rate for lung cancer because of persistently low patient survival (Fig. 1b) [1]. There are two major forms of lung cancer: small cell lung cancer (SCLC), representing approximately 20 %, and non-small cell lung cancer (NSCLC) which accounts for the remaining 80 % of lung cancers (Fig.…”

“…There are two major forms of lung cancer: small cell lung cancer (SCLC), representing approximately 20 %, and non-small cell lung cancer (NSCLC) which accounts for the remaining 80 % of lung cancers (Fig. 1c) [1][2][3]. Histologically, NSCLC can further be classified into adenocarcinoma, which is the most prevalent form (40 % prevalence), followed by squamous cell carcinoma (25 % prevalence), and large cell carcinoma which represents only 10 % of the cases [1,3,4].…”