| Background:Hepatocellular carcinoma(HCC)is considered to be the sixth most common malignant tumor and the fourth leading cause of cancer-related death in the world.Immunotherapy has achieved certain success in advanced liver cancer,but a variety of immune checkpoint inhibitors(ICB)are still not catch the ideal outcome.There is an urgent need for searching for appropriate specific markers to screen patients who are more likely to benefit from immunotherapy.Necroptosis is a way of programmed cell death.The expression of key regulatory factors in the pathway is generally down-regulated in many cancer cells,suggesting that cancer cells may survive by avoiding Necroptosis.Long non-coding RNA(lncRNA)is one of the most common non-coding RNA,which can affect the biological process by regulating transcriptional or post-transcriptional mechanisms.However,there are few studies on necroptosis related lncRNA in hepatocellular carcinoma.In this study,bioinformatics methods were used to screen the lncRNA which was significantly related to the prognosis of patients diagnosed with liver cancer,we construct a prognostic model with good predictive performance,predicting the overall survival time of patients,IC50 was used to analyze chemosensitivity.The efficacy of immunotherapy by immune correlation analysis,so as to provide reference for clinical treatment decision-making.Method:The gene transcriptome data and corresponding clinicopathological information of 374 cases of HCC and 50 normal samples were downloaded from The Cancer Genome Atlas(TCGA)database.A total of 377 samples were included in the clinical correlation analysis,and 376 samples were analyzed for follow-up survival.The lncRNA related to necroptosis was obtained by pearson correlation analysis with necroptosis-related genes.In the unsupervised consensus clustering analysis,kappa=2 was chosen as the best cluster number.The prognosis lncRNA were obtained by Cox regression analysis.Ultimately,10 lncRNA significantly related to prognosis were obtained by Lasso-Cox stepwise regression analysis,from which the risk model was constructed,and the risk score of high-risk group and low risk group was calculated by formula.The 50%inhibitory concentration(IC50)of the chemotherapeutic drugs was calculated to evaluate the drug sensitivity.The difference of 22 kinds of immune cell infiltration level and the expression of immune checkpoint molecular were analyzed to evaluate the efficacy of immunotherapy.Construction of a clinical prognosis nomogram to predict the overall survival(OS)of patients with HCC.Kyoto Encyclopedia of Gene and Genome(KEGG)analysis,GO analysis and Gene Enrichment Analysis(GSEA)were applied to evaluate the potential biological function of prognosis necroptosis-related lncRNA,and the receiver operating characteristic curve(ROC)was used to evaluate the reliability of result.Normal liver cell line L-O2 and liver cancer cell line HepG2,Hep3B,LM3 and Huh7 were used to verify the model in vitro.Result:In this study,58 prognosis necroptosis-related lncRNA were identified.Bioinformatics analysis showed that prognosis-related lncRNA were highly expressed in HCC tissue.Compared with the low risk group,high risk group is characterized by shorter OS,higher histological grade and later pathological stage.Risk score is qualified to act as an independent prognostic factor to predict OS in HCC patients with high accuracy.In case of the tumor immune microenvironment,the infiltration level of activated natural killer(NK)cells was lower in high risk group,furthermore,it was negatively correlated with risk score.The expression level of immune checkpoint molecules was higher in high-risk group.Patients in the high-risk group were more sensitive to most common chemotherapeutic drugs.Conclusion:In this study,we constructed a prognostic risk model,encompassing 10 necroptosis-related lncRNA,which is valuable for survival prediction and predicting tumor microenvironment and further guiding immunotherapy,expecting to be a prognostic marker for HCC. |
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