Identification of novel gene expression signature in lung adenocarcinoma by using next-generation sequencing data and bioinformatics analysis

Abstract

// Ya-Ling Hsu 1, * , Jen-Yu Hung 2, 3, * , Yen-Lung Lee 4 , Feng-Wei Chen 5 , Kuo-Feng Chang 6 , Wei-An Chang 3, 5 , Ying-Ming Tsai 1, 3 , Inn-Wen Chong 3, 7 and Po-Lin Kuo 5, 8, 9 1 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 4 Division of Thoracic surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 5 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Welgene Biotech. Inc, Taipei, Taiwan 7 Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Inn-Wen Chong, email: chong@kmu.edu.tw Po-Lin Kuo, email: kuopolin@seed.net.tw Keywords: next-generation sequencing, bioinformatics, microRNA, messenger RNA, lung adenocarcinoma Received: July 31, 2017      Accepted: August 28, 2017      Published: September 18, 2017 ABSTRACT Lung adenocarcinoma is one of the leading causes of cancer-related death worldwide. We showed transcriptomic profiles in three pairs of tumors and adjacent non-tumor lung tissues using next-generation sequencing (NGS) to screen protein-coding RNAs and microRNAs. Combined with meta-analysis from the Oncomine and Gene Expression Omnibus (GEO) databases, we identified a representative genetic expression signature in lung adenocarcinoma. There were 9 upregulated genes, and 8 downregulated genes in lung adenocarcinoma. The analysis of the effects from each gene expression on survival outcome indicated that 6 genes (AGR2, SPDEF, CDKN2A, CLDN3, SFN, and PHLDA2) play oncogenic roles, and 7 genes (PDK4, FMO2, CPED1, GNG11, IL33, BTNL9, and FABP4) act as tumor suppressors in lung adenocarcinoma. In addition, we also identified putative genetic interactions, in which there were 5 upregulated microRNAs with specific targets - hsa-miR-183-5p-BTNL9, hsa-miR-33b-5p-CPED1, hsa-miR-429-CPED1, hsa-miR-182-5p-FMO2, and hsa-miR-130b-5p-IL33. These 5 microRNAs have been shown to be associated with tumorigenesis in lung cancer. Our findings suggest that these genetic interactions play important roles in the progression of lung adenocarcinoma. We propose that this molecular change of genetic expression may represent a novel signature in lung adenocarcinoma, which may be developed for diagnostic and therapeutic strategies in the future.