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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01105

Up-regulation of hsa_circ_0000517 predicts adverse prognosis of hepatocellular carcinoma

 Tao Chen1*, Xicheng Wang1,  Xining Wang1, Wenxin Li1, Qi Zhang2 and  Jie Chen1*
  • 1Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, China
  • 2Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, China

Although huge progress has been made in therapeutics against hepatocellular carcinoma (HCC) over the decades, the prognosis of this lethal disease remains poor. To find out risk factors for HCC-related outcome and better predict the prognosis, there is an unmet need to identify novel biomarkers of HCC. Accumulating evidence suggests that circRNAs play pivotal roles in carcinogenesis of several malignancies. In this study, we analyzed two datasets (GSE 94508 and GSE 97332) to examine differentially expressed circRNAs markedly related to HCC pathogenesis. Using Limma package in R and WGCNA analysis, hsa_circ_0000517 was significantly up-regulated in HCC (adjusted P <0.01). Thereafter, a hsa_circ_0000517-related regulatory network was built based on application of databases including CSCD, TargetScan, miRDB, and miRTarBase. We uncovered the potential function of hsa_circ_0000517 through bioinformatics approaches, such as PPI network, GO, and KEGG pathway analysis. Specifically, functional analysis unveiled that hsa_circ_0000517 was likely to regulate the MAPK and Ras pathway through sponging several miRNAs and having an impact on the expression of TP53, MYC, and AKT1. To verify our initial finding, the expression of hsa_circ_0000517 in 60 HCC patients was detected by qRT-PCR and the expression in cancer tissues was higher compared with the paracarcinoma tissues. Survival analysis suggests high hsa_circ_0000517 expression was associated with adverse prognosis in HCC patients. Furthermore, this circRNA was significantly up-regulated in worse TNM stage, consistent with the progressive-stage-specific characteristic of circRNAs. A prognostic nomogram built on AFP and has_circ_0000517 showed significant diagnostic value. In all, we concluded that hsa_circ_0000517, a promising molecular in underlying mechanism of HCC, is a potent valuable biomarker for prognosis prediction.

Keywords: hsa_circ_0000517, Hepatocellular Carcinoma, CircRNAs, bioinformatics, GEO

Received: 15 Aug 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Chen, Wang, Wang, Li, Zhang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Tao Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Guangzhou, China,
Dr. Jie Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Guangzhou, China,