机构：[1]Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming,Yunnan Province, the People's Republic of China昆明医科大学附属第一医院医学检验科医技科室[2]Yunnan Institute of Laboratory Diagnosis, Kunming,Yunnan Province, the People's Republic of China[3]Yunnan Key Laboratory of Laboratory Medicine,Kunming, Yunnan Province, the People's Republic of China[4]Department of Pathology, First AffiliatedHospital of Kunming Medical University, Kunming, Yunnan Province, the People's Republic of China医技科室病理科昆明医科大学附属第一医院[5]Department of Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas,United States of America[6]Department of Thoracic Surgery, First Affiliated Hospital of Kunming MedicalUniversity, Kunming, Yunnan Province, the People's Republic of China外科科室胸外科昆明医科大学附属第一医院[7]Department of Biological Sciences,University of Wisconsin-Parkside, Somers, Wisconsin, United States of America
Objectives Lung cancer in Xuanwei (LCXW), China, is known throughout the world for its distinctive characteristics, but little is known about its pathogenesis. The purpose of this study was to screen potential novel "driver genes" in LCXW. Methods Genome-wide DNA copy number alterations (CNAs) were detected by array-based comparative genomic hybridization and differentially expressed genes (DEGs) by gene expression microarrays in 8 paired LCXW and non-cancerous lung tissues. Candidate driver genes were screened by integrated analysis of CNAs and DEGs. The candidate genes were further validated by real-time quantitative polymerase chain reaction. Results Large numbers of CNAs and DEGs were detected, respectively. Some of the most frequently occurring CNAs included gains at 5p15.33-p15.32, 5p15.1-p14.3, and 5p14.3-p14.2 and losses at 11q24.3, 21q21.1, 21q22.12-q22.13, and 21q22.2. Integrated analysis of CNAs and DEGs identified 24 candidate genes with frequent copy number gains and concordant upregulation, which were considered potential oncogenes, including CREB3L4, TRIP13, and CCNE2. In addition, the analysis identified 19 candidate genes with a negative association between copy number change and expression change, considered potential tumor suppressor genes, including AHRR, NKD2, and KLF10. One of the most studied oncogenes, MYC, may not play a carcinogenic role in LCXW. Conclusions This integrated analysis of CNAs and DEGs identified several potential novel LCXW-related genes, laying an important foundation for further research on the pathogenesis of LCXW and identification of novel biomarkers or therapeutic targets.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81160292, 81460325, 81660388]; High Level Talents of Health Technology in Yunnan Province [L-201202]; Key Project for Applied Basic Research in Yunnan Province [2014FA014]
第一作者机构：[1]Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming,Yunnan Province, the People's Republic of China[2]Yunnan Institute of Laboratory Diagnosis, Kunming,Yunnan Province, the People's Republic of China[3]Yunnan Key Laboratory of Laboratory Medicine,Kunming, Yunnan Province, the People's Republic of China
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推荐引用方式(GB/T 7714)：
Zhang Yanliang,Xue Qiuyue,Pan Guoqing,et al.Integrated Analysis of Genome-Wide Copy Number Alterations and Gene Expression Profiling of Lung Cancer in Xuanwei, China[J].PLOS ONE.2017,12(1):doi:10.1371/journal.pone.0169098.
APA：
Zhang, Yanliang,Xue, Qiuyue,Pan, Guoqing,Meng, Qing H.,Tuo, Xiaoyu...&Duan, Yong.(2017).Integrated Analysis of Genome-Wide Copy Number Alterations and Gene Expression Profiling of Lung Cancer in Xuanwei, China.PLOS ONE,12,(1)
MLA：
Zhang, Yanliang,et al."Integrated Analysis of Genome-Wide Copy Number Alterations and Gene Expression Profiling of Lung Cancer in Xuanwei, China".PLOS ONE 12..1(2017)
