Abstract

PurposeHepatocellular carcinoma (HCC) is the seventh most commonly diagnosed cancer and the fourth-leading cause of cancer-related death worldwide. Chronic hepatitis B virus (HBV) is the leading cause of HCC in China. Emerging evidence suggests that long noncoding (lnc)-RNAs are deregulated and are involved in the development of HCC. Our previous study found that HBV X protein can promote HCC by altering lncRNA expression profiles. The purpose of this study was to investigate the expression of the lncRNA semaphorin 6A–antisense RNA 1 (SEMA6A-AS1) and its prognostic value in HBV-related HCC. MethodsSamples of HCC tissues and adjacent nontumor tissues were collected from patients who were pathologically diagnosed with HBV-related HCC after hepatectomy. Eligible patients had not received preoperative radiotherapy, chemotherapy, or embolotherapy. Real-time quantitative reverse-transcription polymerase chain reaction was performed to evaluate the expression levels of SEMA6A-AS1 in all tissue specimens. The correlations between SEMA6A-AS1 expression and clinicopathologic characteristics were analyzed using the χ2 test and the Fisher exact test. Overall survival curves constructed by the Kaplan–Meier method and univariate analysis made by Cox proportional hazards modeling were used for determining the prognostic significance of SEMA6A-AS1. FindingsSpecimens were collected from 47 patients (45 men, 2 women; mean age, 48.4 [10.7] years). SEMA6A-AS1 expression was significantly downregulated in HBV-related HCC tissues compared with that in adjacent noncancerous hepatic tissues (P < 0.01). Low levels of SEMA6A-AS1 were correlated with high α-fetoprotein level (P = 0.002), high Edmondson-Steiner tumor grade (P = 0.047), high tumor node metastasis stage (P = 0.01), capsular invasion (P = 0.005), and poor clinical response (P = 0.002). Additionally, both Kaplan–Meier estimator and univariate Cox regression analysis revealed that low SEMA6A-AS1 expression was significantly associated with poor overall survival (P < 0.05). ImplicationsThe results show that low expression of SEMA6A-AS1 was associated with a poor prognosis in patients with HBV-related HCC. It is necessary to determine the function and mechanism of SEMA6A-AS1 in HCC in order to identify it as a prognostic biomarker and therapeutic target.

Highlights

  • Hepatocellular carcinoma (HCC) is the seventh most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.[1]

  • Specimens were collected from 47 patients (45 men, 2 women; mean age, 48.4 [10.7] years)

  • It is important to study the molecular mechanism of hepatocarcinogenesis, and to identify effective prognostic biomarkers for improving clinical diagnosis and management of patients with HCC

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the seventh most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.[1] Despite therapeutic. Long noncoding (lnc)-RNAs are a subgroup of noncoding RNAs that contain >200 nucleotides and lack the capability of coding protein.[3] Emerging evidence suggests that lncRNAs are involved in cancer pathogenesis and progression via regulating transcription and epigenetics.[4] Several lncRNAs, such as p53-stabilizing and activating RNA (PSTAR),[5] differentiation-antagonizing noneprotein coding RNA (DANCR),[6] long intergenic noneprotein coding RNA (LINC)-1138,7 hepatocellular carcinoma up-regulated long noncoding RNA (HULC),[8] and TP73-AS1,9 are dysregulated and are involved in HCC development and progression.[10] In China, chronic hepatitis B virus (HBV) and subsequent liver fibrosis and cirrhosis are the leading causes of HCC. Studies have found that HBx can promote HBV-related HCC via regulation of a series of lncRNAs, such as lncRNA-6195,12 down-regulated expression by HBx (DREH),[13] Unigene56159,14 and urothelial cancereassociated RNA (UCA)-1.15 the functions and mechanisms of most HBx-related lncRNAs in HCC are still unclear

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