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DNA methylation-based diagnostic and prognostic biomarkers of nonsmoking lung adenocarcinoma patients
Authors:Xiaoming Zhang  Chundi Gao  Lijuan Liu  Chao Zhou  Cun Liu  Jia Li  Jing Zhuang  Changgang Sun
Institution:1. College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, PR China;2. College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, PR China;3. Department of Traditional Chinese Medicine Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong, PR China

Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, PR China;4. School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, PR China;5. Department of Traditional Chinese Medicine Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong, PR China;6. Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, PR China

Abstract:Currently, there are few studies on patients with nonsmoking lung adenocarcinoma, and the pathogenesis is still unclear. The role of DNA methylation in the pathogenesis of cancer is gradually being recognized. The purpose of this study was to determine the abnormal methylation genes and pathways involved in nonsmoking lung adenocarcinoma patients. Gene expression microarray data (GSE10072, GSE43458) and gene methylation microarray data (GSE62948) were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes were obtained through GEO2R. Next, we analyzed the function and enrichment of the selected genes using Database for Annotation, Visualization, and Integrated Discovery. The protein-protein interaction (PPI) networks were constructed using the Search Tool for the Retrieval of Interacting Genes database and visualized in Cytoscape. Finally, we performed module analysis of the PPI network using Molecular Complex Detection. And we obtained 10 hub genes by Cytoscape Centiscape. We analyzed the independent prognostic value of each hub gene in nonsmoking nonsmall cell lung cancer patients through Kaplan-Meier plotter. Seven hub genes (CXCL12, CDH1, CASP3, CREB1, COL1A1, ERBB2, and ENO2) were closely related to the overall survival time. This study provides an effective bioinformatics basis for further understanding the pathogenesis and prognosis of nonsmoking lung adenocarcinoma patients. Hub genes with prognostic value could be selected as effective biomarkers for timely diagnosis and prognostic of nonsmoking lung adenocarcinoma patients.
Keywords:bioinformatics  expression  gen  lung adenocarcinoma  methylation
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