Abstract
ObjectivesLung 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.MethodsGenome-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.ResultsLarge 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.ConclusionsThis 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.
Highlights
Lung cancer is the leading cause of cancer mortality worldwide
Candidate driver genes were screened by integrated analysis of copy number alterations (CNAs) and differentially expressed genes (DEGs)
The indoor air concentrations of particulate matter and extractable organic matter may reach as high as 24.4 mg/m3 and 17.6 mg/m3, respectively, and the corresponding benzo[a]pyrene concentration, an indicator of carcinogenic polycyclic aromatic hydrocarbons (PAHs), can reach as high as 19.3 μg/m3 which is comparable to exposure levels experienced by coke oven workers [4]
Summary
Lung cancer is the leading cause of cancer mortality worldwide. It is the fastest-increasing cancer in China and has been the leading cause of cancer death in China since 2004 [1]. The incidence of lung cancer is high in some regions of the country, such as Xuanwei and Gejiu. Xuanwei City (formerly known as Xuanwei County) is located in the northeast of Yunnan Province, China. It is 102 km from east to west, and 91 km from north to south, with a total area of 6,257 km. The morbidity and mortality rates of lung cancer in Xuanwei are the highest in China and have shown clear upward trends since the mid-1970s [2]. The indoor air concentrations of particulate matter and extractable organic matter may reach as high as 24.4 mg/m3 and 17.6 mg/m3, respectively, and the corresponding benzo[a]pyrene concentration, an indicator of carcinogenic polycyclic aromatic hydrocarbons (PAHs), can reach as high as 19.3 μg/m3 which is comparable to exposure levels experienced by coke oven workers [4]
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