Identification and validation of a five-necroptosis-related lncRNAs signature for prognostic prediction in hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is one of the most common digestive malignant tumors with poor prognosis. As a kind of death receptor-mediated regulated programmed death, necroptosis has the dual characteristics of necrosis and apoptosis. Long non-coding RNAs (lncRNAs) are reported to be key regulators in tumor necroptosis. This study aimed to identify the necroptosis-related lncRNAs (np-lncRNA) in HCC and investigate their relationships with prognosis. Method The RNA-sequencing data and clinicopathological and survival information of patients with HCC were retrieved from The Cancer Genome Atlas (TCGA) database. The np-lncRNAs were analyzed to predict the prognosis of patients with HCC. Stepwise multivariate Cox regression analysis was used to construct prognostic signatures related to necroptosis. Kaplan-Meier (KM) analysis was used to compare the prognosis of patients. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) was used to assess the accuracy of the prognostic signature. Quantitative real-time polymerase chain reaction(qPCR) was used to validate the lncRNAs expression among samples from an independent cohort. Results The np-lncRNAs ZFPM2-AS1, AC099850.3, BACE1-AS, KDM4A-AS1 and MKLN1-AS were identified as potential prognostic biomarkers. The area under the curve (AUC) of the prognostic signature constructed by these np-lncRNAs reached 0.773. Patients were divided into two groups based on the risk score calculated by the signature, and poorer overall survival was shown in the high-risk group. Gene Set Enrichment Analysis (GSEA) suggested that tumor-related pathways (mTOR, MAPK and p53 signaling pathways) and immune-related functions (T cell receptor signaling pathway and natural killer cell mediated cytotoxicit) were significantly different between the low risk and high risk group. The increased expression of np-lncRNAs was confirmed in another independent HCC cohort. Conclusions This signature is a reliable tool for predicting the prognosis of HCC patients. Our findings provide a subset of np-lncRNA biomarkers for prognosis prediction and personalized treatment of HCC patients.