Integrated analysis identifies a long non-coding RNAs-messenger RNAs signature for prediction of prognosis in hepatitis B virus-hepatocellular carcinoma patients

Abstract

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), but HBV-HCC related prognosis signature remains rarely investigated. This study was to identify an integrated long non-coding RNAs-messenger RNAs (lncRNA-mRNA) signature for prediction of overall survival (OS) and explore their underlying functions. One RNA-sequencing dataset (training set, n = 95) and one microarray dataset E-TABM-36 (validation set, n = 44) were collected. Least absolute shrinkage and selection operator analysis was performed to identify an lncRNA-mRNA prognosis signature. The OS difference of patients in the high-risk and low-risk risk groups was evaluated by Kaplan–Meier curve. Area under the receiver operating characteristic curve (AUC), Harrell concordance index (C-index) calculation, and multivariate analyses with clinical characteristics were used to determine the prognostic ability. Furthermore, a coexpression network was constructed to interpret the functions. Nine signature genes (3 lncRNAs and 6 mRNAs) were selected to generate the risk score model. Patients belonging to the high-risk group showed a significantly shorter survival than those of the low-risk group. The prediction accuracy of the risk score for 5-year OS was 0.936 and 0.905 for the training set and validation set, respectively. Also, this risk score was independent of various clinical variables for the prognosis prediction. Incorporation of the risk score remarkably increased the predictive power of the routine clinical prognostic factors (vascular invasion status, tumor recurrence status) (AUC = 0.942 vs 0.628; C-index = 0.7997 vs 0.6908). Furthermore, LncRNA insulin-like growth factor 2 antisense RNA (IGF2-AS) and long intergenic non-protein coding RNA 342 (LINC00342) were predicted to exert tumor suppression effects by regulating homeobox D1 (HOXD1) and secreted frizzled related protein 5 (SFRP5), respectively; while lncRNA rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) may possess carcinogenic potential by promoting the transcription of chromobox 2 (CBX2), cell division cycle 20 (CDC20), matrix metallopeptidase 12 (MMP12), stratifin (SFN), tripartite motif containing 16 (TRIM16), and uroplakin 3A (UPK3A). These mRNAs may be associated with cell proliferation or apoptosis related pathways. This study may provide a novel, effective prognostic biomarker, and some therapeutic targets for HBV-HCC patients.

TRIM proteins in hepatocellular carcinoma

“…LncRNA XIST directly targets miR-192 to up-regulate TRIM25 [ 60 ]. LncRNA rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) promotes TRIM16 expression [ 61 ]. LncRNA RP11-286H15.1 binds to poly(A) binding protein 4 (PABPC4) and promotes its ubiquitin degradation.…”

The development and validation of a novel senescence-related long-chain non-coding RNA (lncRNA) signature that predicts prognosis and the tumor microenvironment of patients with hepatocellular carcinoma

“…This may help explain why many successful preclinical responses are not reproduced after entering real clinical trials. In addition, compared with other studies using the TCGA database to develop lncRNA prognostic models (13)(14)(15)(16)(17)(18), our HCCSenLncSig model is comparable. This shows that the senescent cells in the TME are helpful in predicting the prognosis of HCC, and are at least as valuable as other biomarkers.…”

“…A high level of LINC00958 aggravated HCC lipogenesis and progression through sponging miR-3619-5p, further upregulating the hepatoma-derived growth factor expression (12). Although several lncRNA prognostic models for HCC have been developed (13)(14)(15)(16)(17)(18), the potential immune microenvironment predictive ability and therapeutic guidance of the models, especially for immunotherapy, have yet to be evaluated.…”

Molecular Analysis of Prognosis and Immune Infiltration of Ovarian Cancer Based on Homeobox D Genes

“…The lncRNA insulin-like growth factor 2 antisense RNA (IGF2-AS) is predicted to exert a tumor suppressive effect by HOXD1 [40]. HOXD3 plays a key role in BRCA stemness and drug resistance through integrin β3-mediated Wnt/βcatenin signaling [41].…”