Identification of lncRNA prognostic signature and analysis of their functions for HCV-related hepatocellular carcinoma

Abstract

Background Hepatitis C virus (HCV) infection is a main contribution to the increase in hepatocellular carcinoma (HCC) incidence and patients’ death recently, but prognostic biomarkers for HCV-related HCC remain rarely reported. This study was to identify an lncRNA prognostic signature for HCV-HCC patients and explore their underlying function mechanisms. Methods In total, 102 HCV-HCC samples and 50 normal control samples were obtained from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis were conducted to screen an lncRNA signature that could predict overall survival (OS) and then, the risk score was calculated using this signature. The prognostic potential of this risk score was evaluated by drawing Kaplan-Meier, receiver operating characteristic (ROC) curves and performing multivariate Cox regression analyses with clinical variables. Furthermore, a co-expression and competing endogenous RNA (ceRNA) networks were constructed to explore the functional mechanisms of lncRNAs. Results Multivariate Cox regression showed six lncRNAs (SLC16A1-AS1, ZFPM2-AS1, JARID2-AS1, LINC01426, USP3-AS1 and LYPLAL1-AS1) were significantly associated with OS of HCV-HCC patients. These six lncRNAs were used to establish a risk score model, which displayed a higher prognosis prediction accuracy [area under the ROC curve (AUC) = 0.95 for training set; AUC = 0.885 for testing; AUC = 0.907 for entire set]. Also, this was independent of various clinical variables. The crucial co-expression (LINC01426/SLC16A1-AS1-AURKA/SFN/CCNB1, ZFPM2-AS1/LYPLAL1-AS1/JARID2-AS1-TSSK6) or ceRNA (USP3-AS1-hsa-miR-383-SFN) interaction axes were identified. Conclusion Our study identified a novel six-lncRNA prognosis signature for HCV-HCC patients and indicated their underlying mechanisms for HCC progression.

The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma

“…Notably, HCC Patients having high LINC01419 and AK021443 expression levels showed significantly lower overall survival as indicated by Kaplan-Meier and Log-rank survival tests. In the same context, it was reported that HCC patients having increased expression levels of AK021443 had shorter OS than those with low AK021443 expression levels, in addition, increased LINC01419 expression was significantly related to a lower OS in HCV-HCC patients [5,31].…”

“…In addition, LINC01419 promotes HCC development and metastasis by directing EZH2-regulated RECK [30,31]. Furthermore, the downregulation of LINC01419 inhibits cell migration, invasion, and autophagy via deactivation of the PI3K/Akt1/mTOR pathway [32].…”