Abstract
The current prognostic long noncoding RNA (lncRNA) signatures for hepatocellular carcinoma (HCC) are still controversial and need to be optimized by systematic bioinformatics analyses with suitable methods and appropriate patients. Therefore, we performed the study to establish a credible lncRNA signature for HCC outcome prediction and explore the related mechanisms. Based on the lncRNA profile and the clinical data of carefully selected HCC patients (n = 164) in TCGA, six of 12727 lncRNAs, MIR22HG, CTC-297N7.9, CTD-2139B15.2, RP11-589N15.2, RP11-343N15.5, and RP11-479G22.8 were identified as the independent predictors of patients' overall survival in HCC by sequential univariate Cox and 1000 times Cox LASSO regression with 10-fold CV, and multivariate Cox analysis with 1000 times bootstrapping. In the Kaplan-Meier analysis with patients trichotomized by the six-lncRNA signature, high-risk patients showed significantly shorter survival than mid- and low-risk patients (log-rank test P < 0.0001). According to the ROCs, the six-lncRNA signature showed superior predictive capacity than the two existing four-lncRNA combinations and the traditional prognostic clinicopathological parameter TNM stage. Furthermore, low MIR22HG and CTC-297N7.9, but high CTD-2139B15.2, RP11-589N15.2, RP11-343N15.5, and RP11-479G22.8, were, respectively, demonstrated to be related with the malignant phenotypes of HCC. Functionally, the six lncRNAs were disclosed to involve in the regulation of multiple cell cycle and stress response-related pathways via mediating transcription regulation and chromatin modification. In conclusion, our study identified a novel six-lncRNA signature for resectable HCC prognosis prediction and indicated the underlying mechanisms of HCC progression and the potential functions of the six lncRNAs awaiting further elucidation.