Systems biology approach to stage-wise characterization of epigenetic genes in lung adenocarcinoma

Abstract

BackgroundEpigenetics refers to the reversible functional modifications of the genome that do not correlate to changes in the DNA sequence. The aim of this study is to understand DNA methylation patterns across different stages of lung adenocarcinoma (LUAD).ResultsOur study identified 72, 93 and 170 significant DNA methylated genes in Stages I, II and III respectively. A set of common 34 significant DNA methylated genes located in the promoter section of the true CpG islands were found across stages, and these were: HOX genes, FOXG1, GRIK3, HAND2, PRKCB, etc. Of the total significant DNA methylated genes, 65 correlated with transcription function. The epigenetic analysis identified the following novel genes across all stages: PTGDR, TLX3, and POU4F2. The stage-wise analysis observed the appearance of NEUROG1 gene in Stage I and its re-appearance in Stage III. The analysis showed similar epigenetic pattern across Stage I and Stage III. Pathway analysis revealed important signaling and metabolic pathways of LUAD to correlate with epigenetics. Epigenetic subnetwork analysis identified a set of seven conserved genes across all stages: UBC, KRAS, PIK3CA, PIK3R3, RAF1, BRAF, and RAP1A. A detailed literature analysis elucidated epigenetic genes like FOXG1, HLA-G, and NKX6-2 to be known as prognostic targets.ConclusionIntegrating epigenetic information for genes with expression data can be useful for comprehending in-depth disease mechanism and for the ultimate goal of better target identification.

A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma

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Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature

“…A systems biology approach was utilized for a stage-wise characterization of epigenetic genes and epigenetic subnetwork analysis identified a set of seven conserved genes across all stages of lung adenocarcinoma (90). The methylation status of HOXD3, ARHGDIB, AGAP2 genes was reported to be involved in cell signaling and cytoskeletal organization in squamous cell lung carcinoma.…”

The homeobox NKX and Neoplasms in Digestive system: a systematic review.

“…It's a transcription factor with known positive and negative regulatory activities in development and differentiation [84] and seemed to be a tumor suppressor [85] . NKX6.2 is respectively detected in a variety of different neoplasms, like brain tumor [86] , bladder cancer [87] , renal cell carcinoma [88][89] , and lung adenocarcinoma [90] . By so far, no NKX6.2 expression is reported in gastrointestinal neoplasms.…”