Abstract

Circular RNAs (circRNAs) represent potential biomarkers because of their highly stable structure and robust expression pattern in clinical samples. The aim of this study was to evaluate the expression of a recently identified circRNA, hsa_circ_0005986; determine its clinical significance; and evaluate its potential as a biomarker of hepatocellular carcinoma (HCC). We evaluated hsa_circ_0005986 expression in 123 HCC tissue samples, its clinical significance, and its association with patients’ clinicopathological characteristics and survival. Hsa_circ_0005986 expression was downregulated in HCC tissues. Low hsa_circ_0005986 expression was more common in tumors larger than 5 cm [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.51–6.76; p = 0.002], advanced TNM stage (III/IV; OR, 2.39; 95% CI, 1.16–4.95; p = 0.018), and higher BCLC stage (B/C; OR, 2.71; 95% CI, 1.30–5.65; p = 0.007). High hsa_circ_0005986 expression was associated with improved survival and was an independent prognostic factor for overall [hazard ratio (HR), 0.572; 95% CI, 0.339–0.966; p = 0.037] and progression-free (HR, 0.573; 95% CI, 0.362–0.906; p = 0.017) survival. Moreover, the circRNA–miRNA–mRNA network was constructed using RNA-seq/miRNA-seq data and clinical information from TCGA-LIHC dataset. Our findings indicate a promising role for hsa_circ_0005986 as a prognostic biomarker in patients with HCC.

Highlights

  • Abbreviations CircRNA Circular RNA HCC Hepatocellular carcinoma odds ratio (OR) Odds ratio confidence interval (CI) Confidence interval hazard ratio (HR) Hazard ratio MiRNA MicroRNA miRNA response elements (MREs) MiRNA response element epithelial–mesenchymal transition (EMT) Epithelial-mesenchymal transition computed tomography (CT) Computed tomography

  • Because of the poor prognosis associated with HCC, the identification of biomarkers is essential for predicting patient prognosis and survival and tumor recurrence as well as for determining suitable treatment options

  • Liver disease was primarily caused by hepatitis B (61.0%), alcohol consumption (25.2%), hepatitis C (8.9%), or hepatitis B and C virus co-infection (1.6%)

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Summary

Introduction

Abbreviations CircRNA Circular RNA HCC Hepatocellular carcinoma OR Odds ratio CI Confidence interval HR Hazard ratio MiRNA MicroRNA MRE MiRNA response element EMT Epithelial-mesenchymal transition CT Computed tomography. Circular RNAs (circRNAs) are a class of highly stable, single-stranded RNAs that form a loop through covalent binding. They are synthesized either from coding or noncoding genomic regions. In contrast to linear RNAs, circRNAs are formed through a back-splicing event, which occurs via the linkage of downstream 3′ and upstream 5′ splice sites to form covalent and canonical b­ onds[6]. Exons, introns, or both may serve as substrates for circRNA back-splicing. Pre-tRNA splicing into two parts by specific enzymes gives rise to tRNA and tricRNA—a unique class of c­ iRNA12

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