Identification of novel gene expression signature in lung adenocarcinoma by using next-generation sequencing data and bioinformatics analysis
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Ya-Ling Hsu1,*, Jen-Yu Hung2,3,*, Yen-Lung Lee4, Feng-Wei Chen5, Kuo-Feng Chang6, Wei-An Chang3,5, Ying-Ming Tsai1,3, Inn-Wen Chong3,7 and Po-Lin Kuo5,8,9
1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
4Division of Thoracic surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
6Welgene Biotech. Inc, Taipei, Taiwan
7Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
8Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan
9Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan
*These authors have contributed equally to this work
Inn-Wen Chong, email: email@example.com
Po-Lin Kuo, email: firstname.lastname@example.org
Keywords: next-generation sequencing, bioinformatics, microRNA, messenger RNA, lung adenocarcinoma
Received: July 31, 2017 Accepted: August 28, 2017 Published: September 18, 2017
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.
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