Construction Of Liver Cancer Prognosis Model And Immune Process Research Based On Ferroptosis-related Gene Expression Characteristic

Background:(HCC)is a malignant disease with significant heterogeneity which makes it difficult for clinicians to predict the overall survival of patient.Previous studies have shown that the targeted therapy drug sorafenib can induce ferroptosis in hepatocellular carcinoma cells,which is an iron-dependent programmed cell death with accumulation of intracellular lipid reactive oxygen species(ROS).However,the prediction performance of ferroptosis associated genes in predicting the prognosis of hepatocellular carcinoma patients remains to be further elucidated.Method:In our research,we accessed mRNA data file and corresponding clinical profiles of hepatocellular carcinoma patients from the neoplasm databases TCGA and ICGC.A polygenic trait prognostic model was constructed in the TCGA cohort using a(LASSO)Cox regression model.Furthermore,we used the ICGC cohort of hepatocellular carcinoma patients as a validation set to verify the predictive performance of the model.Results:Our experimental results showed that in the TCGA cohort,most(about 85 per cent)ferroptosis-associated genes(FAGs)were expressed with significant differences between HCC tissues and adjacent normal liver tissues(P value<0.05).A genetic featurebased prognostic prediction model composed of 7 ferroptosis-related genes was constructed,and patients were classified into two parts:high risk and low risk group.Compared with the OS status in the low-risk group,patients in the high-risk group showed significantly lower overall survival(OS)(P value<0.001 in the TCGA set and P<0.001 in the ICGC set).We used the method of multivariate COX regression analysis,risk score has been confirmed as an independent predictor of overall survival(HR>1,P<0.01).Receiver operating characteristic(ROC)analysis proved the ability of this ferroptosis-related gene expression model for predicting disease prognosis.Subsequent gene function analysis revealed that immunerelated pathways were enriched and immune status differed between the two risk groups.Conclusion:In conclusion,this new ferroptosis-related gene model could serve as a tool to predict the prognosis of patients with hepatocellular carcinoma.Targeted therapy for ferroptosis may be a treatment option for hepatocellular carcinoma patients.Background:Ferroptosis is an iron-dependent programmed cell death process,and studies have confirmed that it plays an important regulatory role in the occurrence and development of various malignant tumors including hepatocellular carcinoma(HCC).In addition,the role of abnormally expressed long non-coding RNAs(lncRNAs)in regulating and driving the occurrence and development of hepatocellular carcinoma has attracted more and more researchers’ attention.However,there is still a lack of research on the role of ferroptosis-related lncRNAs in the prognosis prediction of HCC patients.Method:In this study,we used the Pearson test method to analyze the association between differentially expressed lncRNAs and ferroptosis-related genes in hepatocellular carcinoma tissues and normal tissues obtained from The Cancer Genome Atlas(TCGA),and found 68 aberrantly expressed and prognosisrelated ferroptosis-related lncRNAs.Based on this,we established an HCC prognosis prediction model composed of 12 ferroptosis-related lncRNA expression signatures.In addition,HCC patients were divided into high-risk group and low-risk group according to the risk score of this 12 ferroptosis-related lncRNA expression prognostic model.Gene enrichment analysis indicated that ferroptosis-related lncRNA-based expression signatures may regulate liver cancer immune microenvironment signaling pathways through ferroptosis,chemical carcinogenesis-reactive oxygen species(ROS),and NK cell-mediated cytotoxicity pathways.In addition,immune cell correlation analysis showed that there were significant differences in immune infiltrating cell subtypes,such as helper T cells,macrophages,monocytes,and regulatory T cells between the two groups of patients.In addition,the expression of multiple immune checkpoint molecules was found to be significantly increased in the high-risk group(eg,PD1,CTLA-4,CD86,etc.).Results:Our research provides a new method for predicting prognosis using ferroptosis-related lncRNA expression signature prognostic model in hepatocellular carcinoma.And it provides new approaches and tools for predicting patient response to immunotherapy.Conclusion:In conclusion,ferroptosis-related lncRNA expression signatures can be used to construct a prognostic prediction model to accurately predict the overall survival(OS)of HCC patients,and can be used as an independent influencing factor for patient prognosis.Further analysis showed that ferroptosisrelated lncRNAs may affect the efficacy of immunotherapy in patients with HCC by altering the tumor microenvironment(TME),so this model may serve as an new indicator of the response of hepatocellular carcinoma to immunotherapy.