Yuanyuan Zhao1,2,3,4, Bo Yang1,2,3,4, Dong Chen1,2,3,4, Xiaojun Zhou1,2,3,4, Meixi Wang1,2,3,4, Jipin Jiang1,2,3,4, Lai Wei1,2,3,4, Zhishui Chen1,2,3,4. 1. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 2. Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China. 3. NHC Key Laboratory of Organ Transplantation, Wuhan 430030, China. 4. Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.
Abstract
BACKGROUND: The current study aimed to understand the genetic landscape and investigate the diagnostic and prognostic biomarkers of primary hepatocellular carcinoma (HCC). METHODS: A cohort of 36 Chinese HCC samples with hepatitis B virus (HBV) infection was examined by whole-exome sequencing (WES). Prognosis-related alterations were identified and further verified in the TCGA database and GSE65372 profiles in the GEO database. A Chinese replication cohort of 180 HCC samples with HBV infection was collected to evaluate the candidate genes by immunohistochemical analysis. A receiver operating characteristic (ROC) curve analysis evaluated the prognostic power of candidate genes. Finally, EdU and transwell invasion assay were performed to detect the function of candidate genes. RESULTS: A total of 11 novel genes showed a significant association with HCC in the discovery cohort. The data were verified using the GEO and TCGA databases, and the expression of ARID1A, CSMD1, and SENP was evaluated in the replication cohort. Furthermore, ARID1A, CSMD1, and SENP3 are effective prognostic biomarkers for HCC patients in the replication population. CONCLUSIONS: Molecular heterogeneity was detected in HCC patients, and ARID1A, CSMD1, and SENP3 were identified as effective HCC prognosis biomarkers. CSMD1 prevents HCC by suppressing cell invasion.
BACKGROUND: The current study aimed to understand the genetic landscape and investigate the diagnostic and prognostic biomarkers of primary hepatocellular carcinoma (HCC). METHODS: A cohort of 36 Chinese HCC samples with hepatitis B virus (HBV) infection was examined by whole-exome sequencing (WES). Prognosis-related alterations were identified and further verified in the TCGA database and GSE65372 profiles in the GEO database. A Chinese replication cohort of 180 HCC samples with HBV infection was collected to evaluate the candidate genes by immunohistochemical analysis. A receiver operating characteristic (ROC) curve analysis evaluated the prognostic power of candidate genes. Finally, EdU and transwell invasion assay were performed to detect the function of candidate genes. RESULTS: A total of 11 novel genes showed a significant association with HCC in the discovery cohort. The data were verified using the GEO and TCGA databases, and the expression of ARID1A, CSMD1, and SENP was evaluated in the replication cohort. Furthermore, ARID1A, CSMD1, and SENP3 are effective prognostic biomarkers for HCCpatients in the replication population. CONCLUSIONS: Molecular heterogeneity was detected in HCCpatients, and ARID1A, CSMD1, and SENP3 were identified as effective HCC prognosis biomarkers. CSMD1 prevents HCC by suppressing cell invasion.
Entities:
Keywords:
HBV infection; characteristic molecular heterogeneity; differentially expressed genes; hepatocellular carcinoma; population specific biomarkers
Authors: Liwei Zhang; Lee H Chen; Hong Wan; Rui Yang; Zhaohui Wang; Jie Feng; Shaohua Yang; Siân Jones; Sizhen Wang; Weixin Zhou; Huishan Zhu; Patrick J Killela; Junting Zhang; Zhen Wu; Guilin Li; Shuyu Hao; Yu Wang; Joseph B Webb; Henry S Friedman; Allan H Friedman; Roger E McLendon; Yiping He; Zachary J Reitman; Darell D Bigner; Hai Yan Journal: Nat Genet Date: 2014-06-01 Impact factor: 38.330
Authors: Ella F Gunady; Kathryn E Ware; Sarah Hoskinson Plumlee; Nicolas Devos; David Corcoran; Joseph Prinz; Hrvoje Misetic; Francesca D Ciccarelli; Tara M Harrison; Jeffrey L Thorne; Robert Schopler; Jeffrey I Everitt; William C Eward; Jason A Somarelli Journal: Evol Med Public Health Date: 2022-04-29