Abstract
Studies have demonstrated the prognosis potential of long noncoding RNAs (lncRNAs) for hepatocellular carcinoma (HCC), but specific lncRNAs for hepatitis B virus- (HBV-) related HCC have rarely been reported. This study was aimed at identifying a lncRNA prognostic signature for HBV-HCC and exploring their underlying functions. The sequencing dataset was collected from The Cancer Genome Atlas database as the training set, while the microarray dataset was obtained from the European Bioinformatics Institute database (E-TABM-36) as the validation set. Univariate and multivariate Cox regression analyses identified that eight lncRNAs (TSPEAR-AS1, LINC00511, LINC01136, MKLN1-AS, LINC00506, KRTAP5-AS1, ZNF252P-AS1, and THUMPD3-AS1) were significantly associated with overall survival (OS). These eight lncRNAs were used to construct a risk score model. The Kaplan-Meier survival curve results showed that this risk score can significantly differentiate the OS between the high-risk group and the low-risk group. Receiver operating characteristic curve analysis demonstrated that this risk score exhibited good prediction effectiveness (area under the curve (AUC) = 0.990 for the training set; AUC = 0.903 for the validation set). Furthermore, this lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis after adjusting other clinical characteristics. The crucial coexpression (LINC00511-CABYR, THUMPD3-AS1-TRIP13, LINC01136-SFN, LINC00506-ANLN, and KRTAP5-AS1/TSPEAR-AS1/MKLN1-AS/ZNF252P-AS1-MC1R) or competing endogenous RNA (THUMPD3-AS1-hsa-miR-450a-TRIP13) interaction axes were identified to reveal the possible functions of lncRNAs. These genes were enriched into cell cycle-related biological processes or pathways. In conclusion, our study identified a novel eight-lncRNA prognosis signature for HBV-HCC patients and these lncRNAs may be potential therapeutic targets.
Highlights
Liver cancer, 90% of which is hepatocellular carcinoma (HCC), is one of the most common malignancies and the leading cause of cancer-related deaths worldwide [1, 2]
More and more evidence has highlighted the important roles of long noncoding RNAs in hepatitis B virus- (HBV-)HCC via directly influencing the expression of their neighboring genes or acting as microRNA sponges to negatively regulate the expression of miRNA target genes (competing endogenous RNA hypothesis) [5]
Fan et al demonstrated that the expression of long noncoding RNAs (lncRNAs) n335586 was significantly increased in Hepatitis B virus (HBV)-positive HCC tissues and cells. lncRNA n335586 may contribute to the migration, invasion, and metastasis of HCC cells by facilitating the expression of its host gene creatine kinase, mitochondrial 1A (CKMT1A), through competitively binding to miR-924 [9]. These findings suggest that lncRNAs may be potential therapeutic targets and prognostic biomarkers for HBV-HCC patients
Summary
90% of which is hepatocellular carcinoma (HCC), is one of the most common malignancies and the leading cause of cancer-related deaths worldwide [1, 2]. It may be an important issue to screen prognostic biomarkers and therapeutic targets for patients with HBV-HCC in order to optimize treatment, prevent progression, and improve the prognosis. More and more evidence has highlighted the important roles of long noncoding RNAs (lncRNAs) in HBV-HCC via directly influencing the expression of their neighboring genes (coexpression hypothesis) or acting as microRNA (miRNAs) sponges to negatively regulate the expression of miRNA target genes (competing endogenous RNA (ceRNA) hypothesis) [5]. Chen et al found that LINC01152 was significantly upregulated in HBV-positive HCC tissues and cells treated by HBV X protein (HBx). Overexpression of LINC01152 could increase HCC cell proliferation and promote tumor formation in nude mice by directly binding to the promoter region of interleukin- (IL-) 23 to increase its transcription [6]. Hu et al identified that lncRNA WEE2-AS1 was overexpressed
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