Identification Of Pyrostosis Subtypes And Prognosis Model Of Hepatocellular Carcinoma Based On Pyroptosis-related Genes

BackgroundHepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and mortality rates worldwide.Although some progress has been made in its treatment,its prognosis remains poor.Pyroptosis is a programmed cell death mode.Studying the mechanisms and regulatory factors of cell necroptosis in HCC can help to deepen the understanding of the occurrence and development of HCC and provide new ideas for its treatment and prognosis.However,due to the heterogeneity and complexity of HCC tumor tissue,further research is needed to explore its subtypes of Pyroptosis and their prognostic implications.ObjectiveThe aim of this study is to identify the pyroptosis subtypes of HCC and construct a prognostic model for HCC by identifying pyroptosis-related genes.Studying the pyroptosis subtypes of HCC and their prognostic implications can better guide the treatment and management of HCC patients.Specifically,the research objectives include:identifying pyroptosis-related genes of HCC,identifying pyroptosis subtypes of HCC,exploring the relationship between pyroptosis subtypes of HCC and patient prognosis,constructing a prognostic model for HCC,investigating the clinical and biological significance of the pyroptosis-related prognostic model score,and providing new ideas and methods for the treatment and management of HCC.Methods and results1.Clinical and biological significance of pyroptosis subtypes in HCC patientsThis study collected 61 pyroptosis-related genes and found that 20 genes were differentially expressed between HCC and adjacent tissues.The study identified two pyroptosis subtypes of HCC in 335 patients from the TCGA-LIHC cohort using consensus clustering,and found that the overall survival time differed significantly between different pyroptosis subtypes.Further GSVA enrichment analysis showed that biological processes such as cell cycle and DNA replication were enriched in pyroptosis subtype Ⅱ of HCC samples,while liver-related metabolic pathway activity was downregulated.Somatic mutation analysis revealed that TP53 tumor suppressor gene mutations were more frequent in pyroptosis subtype Ⅱ of HCC samples.The results of the three tumor immune microenvironment analysis algorithms,ESITMATE,CIBERSORT,and ssGSEA,suggest that there are typical differences in the immune microenvironment between HCC pyroptosis subtypes.2.Clinical and biological significance of pyroptosis-related prognostic model in HCC patientsWe confirmed that the pyroptosis subtype is closely related to the prognosis of hepatocellular carcinoma(HCC).In this study,we established a pyroptosis-related prognostic model for HCC using the TCGA-LIHC dataset as a training dataset.Specifically,we identified differentially expressed genes between pyroptosis subtypes in the LIHC cohort,and after consistent screening with random forest,univariate,and Lasso cox,we retained 20 genes as pyroptosis subtype-related genes and constructed a pyroptosis related prognostic model.We established a pyroptosis subtype-related score(PSRS)and validated the predictive power of PSRS for overall survival in two independent external validation cohorts.To improve the clinical utility of the model,we explored the clinical value of PSRS and combined it with clinical parameters to construct a nomogram model.GSVA enrichment analysis showed that different metabolic pathways related to the liver and signaling pathways related to liver cancer were enriched in different PSRS groups.Furthermore,with regard to immune microenvironment analysis,we found,using the CIBERSORT algorithm,that the abundance of MO macrophages in the high-PSRS group was significantly higher than that in the low-PSRS group,while the abundance of Naive B cells and monocytes was significantly lower than that in the low-PSRS group.It is worth mentioning that we used the R package oncoPredict to conduct drug sensitivity analysis and focused on the treatment responses of 65 small-molecule compounds related to PSRS.ConclusionBy using pyroptosis-related genes,this study divided HCC patients into different pyroptosis subtypes,revealing the relationship between pyroptosis subtypes and the prognosis of hepatocellular carcinoma(HCC),and constructing an HCC prognostic model based on pyroptosis-related genes.The model can effectively predict the overall survival of HCC patients and has potential clinical application value.In addition,this study found that different pyroptosis subtypes have different signaling pathway activities and somatic mutation patterns.This study creatively identified a group of potential drug molecules for HCC patients based on PSRS groups,which may provide more treatment options for HCC patients.