Identification of Susceptible Genes for Chronic Obstructive Pulmonary Disease with Lung Adenocarcinoma by Weighted Gene Co-Expression Network Analysis.

Abstract

PurposeChronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD) are common disorders and usually co-exists. However, genetic mechanisms between COPD and LUAD are rarely reported. This study aims to identify susceptible genes of COPD with LUAD.MethodsUsing the published data of GSE106899, co-expression modules were constructed by weighted gene co-expression network analysis (WGCNA). Subsequently, top 50 genes in the most tumor-related module were identified, among which hub genes were selected and validated.ResultsTwenty co-expression modules were constructed on 13,865 genes from 62 lung tissues of COPD patients with or without LUAD, in which one module (blue) was most related to tumorigenesis. Functional enrichment analyses showed that the genes in the blue module were mainly enriched in cell cycle, DNA transcription/replication and cancer pathways, etc. Combined with protein–protein interaction network, MTA1, PKMYT1 and FZR1 genes had the most intramodular connectivity, which were regarded as the hub genes. However, only FZR1 was validated to be overexpressed in lung tissues of COPD with LUAD and cigarette smoke extract-stimulated A549 cells, a human LUAD cell line.ConclusionThis study suggests overexpression of FZR1 may play a key role in the tumorigenesis of LUAD in patients with COPD.