Identification of long noncoding RNAs biomarkers in patients with hepatitis B virus-associated hepatocellular carcinoma

Article type: Research Article

Authors: Mou, Yonghua^a | Wang, Dongguo^{b; *} | Xing, Renwei^a | Nie, Hanqiu^a | Mou, Yiping^c | Zhang, Yang^a | Zhou, Xianfei^a

Affiliations: [a] Department of Hepatobiliary Surgery, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang, China | [b] Department of Clinical Lab Medicine, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang, China | [c] Department of Gastrointestinal Surgery, Zhejiang People’s Hospital, Hangzhou, Zhejiang, China

Correspondence: [*] Corresponding author: Dongguo Wang, 381 Zhongshan Eastern Road, Taizhou, PO Box 318000, Zhejiang, China. Tel.: +86 0576 88598262; E-mail: [email protected].

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancer worldwide and chronic infection of hepatitis B virus (HBV) serve as one of leading causes of HCC. OBJECTIVE: This study aimed to identify the novel long noncoding RNAs (lncRNAs) biomarkers for HBV-associated HCC. METHODS: The lncRNA and mRNA expression profiles of HCC patients with HBV infection were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between HCC and adjacent tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for HCC were identified by using feature selection procedure and classification model. Functional annotation of DEmRNAs co-expressed with these lncRNAs biomarkers were performed. Receiver operating characteristic (ROC) curve and survival analysis of these lncRNAs biomarkers were performed. qRT-PCR validation was performed. RESULTS: A total of 82 DElncRNAs and 805 DEmRNAs between HBV-associated HCC and normal tissues were identified. CAPN10-AS1, LINC01093, RP5-890E16.2, FENDRR and C17orf82 were selected as optimal diagnostic and prognostic lncRNA biomarkers for HBV-associated HCC that were co-expressed with 105, 86, 70, 30 and 1 DEmRNAs, respectively. Based on the DEmRNAs co-expressed with these five lncRNAs biomarkers, Jak-STAT signaling pathway and retinol metabolism were two significantly enriched pathways. The result in qRT-PCR validation were consistent with our analysis based on TCGA, generally. CONCLUSIONS: This study identified five potential lncRNAs biomarkers for HBV-associated HCC with great diagnostic and prognostic value and provided clues for their functions in HBV-associated HCC.

Keywords: Hepatocellular carcinoma (HCC), hepatitis B virus (HBV), biomarker, long noncoding RNAs (lncRNAs)

DOI: 10.3233/CBM-181424

Journal: Cancer Biomarkers, vol. 23, no. 1, pp. 95-106, 2018