A Panel of Genes Identified as Targets for 8q24.13-24.3 Gain Contributing to Unfavorable Overall Survival in Patients with Hepatocellular Carcinoma

作     者：Kun ZHAO Yu ZHAO Jia-yi ZHU Hui DONG Wen-ming CONG Yi YU Hui WANG Zhong-Zheng ZHU Qing XU 

作者机构：Department of Oncology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200072 China Shanghai Clinical College of Anhui Medical University Shanghai 200072 China Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Pathology Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China 

出 版 物：《Current Medical Science》 (当代医学科学（英文）)

年 卷 期：2018年第38卷第4期

页      面：590-596页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学] 

基　　金：This project was supported by grants from the Medical Science and Technology Innovation Fund ofPLA, Nanjing branch, China (No. 14ZD07 08MA023) and Ningbo Nature Science Foundation Program (No. 2009A610126) 

主　　题：chromosome 8 copy number aberration hepatocellular carcinoma prognosis gene expression 

摘      要：Copy number aberrations （CNAs） in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma （HCC）. This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients, and further screen for differentially expressed genes in outcome-related CNAs. Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels, respectively. The correlations between CNAs in 8q and outcomes were analyzed in 66 patients, with a median follow-up time of 45.0 months （range, 2.6-108.6 months）. One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs. Copy number gain in 8q was observed in 22 （33.3%） of the 66 HCC cases. The most recurrent gains （with frequencies 〉20%） were 8q 13.3-21.3, 8q21.3-23.3, 8q23.3-24.13, 8q24.13-24.3, and 8q24.3. Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival （P=0.010）. Multivariate Cox analysis identified 8q24.13- 24.3 gain as an independent prognostic factor for poor overall survival （HR=2.47; 95% CI=1.16-5.26; P=0.019）. A panel of 17 genes within the 8q24.13-24.3 region, including ATAD2, SQLE, PVT1, ASAP1, and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without. These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients, and the potential oncogenes ATAD2, SQLE, PVT1, ASAP1, and NDRG1 within the regional gain, may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.