Research Paper|Volume 13, Issue 3|pp 4696—4712

Combined identification of ARID1A, CSMD1, and SENP3 as effective prognostic biomarkers for hepatocellular carcinoma

Yuanyuan Zhao^1,^2,^3,⁴, Bo Yang^1,^2,^3,⁴, Dong Chen^1,^2,^3,⁴, Xiaojun Zhou^1,^2,^3,⁴, Meixi Wang^1,^2,^3,⁴, Jipin Jiang^1,^2,^3,⁴, Lai Wei^1,^2,^3,⁴, Zhishui Chen^1,^2,^3,⁴

¹Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
²Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China
³NHC Key Laboratory of Organ Transplantation, Wuhan 430030, China
⁴Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China

* Equal contribution

Received: June 18, 2020Accepted: December 9, 2020Published: February 7, 2021

https://doi.org/10.18632/aging.202586

Copyright: © 2021 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.