Necroptosis-related lncRNAs and Hepatocellular Carcinoma Undoubtedly Secret

Abstract

Background: The current study demonstrates that necroptosis is an important mechanism of carcinogenesis. However, the predictive value of necroptosis-associated long non-coding RNAs (LncRNAs) in hepatocellular carcinoma has not been demonstrated. The purpose of this study is to apply necroptosis-related lncRNAs to construct a predictive signature to predict the prognosis of hepatocellular carcinoma patients.Methods: The clinical and RNA-seq data were downloaded using The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox analysis was used to screen out suitable necroptosis-related lncRNAs, and then predictive signature was constructed. The TCGA data were randomly divided into high- and low-risk groups, and the Kaplan-Meier method was used to analyze the overall survival (OS) of the two groups to verify the predictive signature. Finally, a prognostic correlation model for predicting disease-freesurvival （DFS）in hepatocellular carcinoma（HCC） was constructed and validated.Results: We had screened out 9 necroptosis-related lncRNAs (BACE1-AS, LINC01188, LUCAT1, PI3KCD-AS2, Z83851.1, AC009283.1, AC012360.2, AC015908.3, AC103760.1), which were used to construct a predictive signature, and draw the receiver operating characteristic (ROC) curve by the high- and low-risk group. It was found that the area under the curve (AUC) of risk score was 0.874, and the AUCs values of 1-,3-,and 5-years were 0.8, 0.759, 0.787. The TCGA data were randomly divided into two cohorts. In two cohorts, The OS of the high-risk groups were significantly lower than that of the low-risk groups, and the AUC of the ROC curves of the two cohorts were 0.851, 0.804, 0.802 and 0.735, 0.716, 0.76 at 1-, 3-, and 5-years. After quantifying immune cell subsets and related functions, it was found that the infiltration of active dendritic cells (aDCs), macrophages, mast cells, natural killer cells (NK), T regulatory cells (Tregs) were significantly different, and the expressions of immune checkpoints CD86, LAIR1, CTLA4, VTCN1, TNFRSF18, CD80, CD276, HHLA2, TNFSF4, TNFRSF8, TNFRSF4, TNFRSF9, LGALS9, HAVCR2 and TNFSF15 were also significantly different.Conclusion: This predictive signature can accurately predict the prognosis of hepatocellular carcinoma patients and provide guidance for the clinical treatment of hepatocellular carcinoma patients.

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

“…Recent evidence suggests that RNA processing has been consistently changed in cancer [ 55 , 56 , 57 ], revealing the critical role of RNA in tumor genesis and cancer development [ 54 , 58 ]. The long noncoding RNAs (lncRNAs) are mainly categorized according to their positional relationship with adjacent coding genes [ 59 ]. Several reports have been published in the scientific literature, highlighting a potential role for lncRNAs in tissue pathophysiology and development [ 20 , 49 , 60 , 61 ].…”