Study on stemness typing and prognostic gene GSDMC of hepatocellular carcinoma
Objective:To screen the patients with hepatocellular carcinoma who are more responsive to immunotherapy by stemness typing,and to verify the prognosis related gene GSDMC.Methods:Twenty-six stem cell genomes were extracted from the StemChecker database,consensus clustering algorithm was applied for the identification of stemness subtypes on 328 hepato-cellular carcinoma samples from The Cancer Genome Atlas Program databases.The differences in prognosis,tumor microenviron-ment components,and treatment response between the two subtypes were assessed.Then,a stem risk model was constructed by integrating weighted gene correlation network analysis,Cox regression and random survival forest analyses.Finally,the prognostic-related gene GSDMC was selected for experimental validation.Results:Based on single-sample gene set enrichment analysis enrichments scores,hepatocellular carcinoma patients were classified into two subtypes(C1 and C2).There were signifi-cant differences in survivalrate,the levels of immune infiltration,and treatment reponse between C1 and C2.Integrating WGC-NA,Cox regression and random forest survival analyses identified four prognostic-related genes(GSDMC,AOC1,OTX1,CASC9).Immunohistochemistry and real-time-quantitative polymerase chain reaction showed that the expression of GSDMC was decreased in hepatocellular carcinoma tissues and cells.Sphere formation assay showed that GSDMC suppressesed hepatocellular carcinoma cells stemness.Conclusion:The identification of two distinct stem cell subtypes,C1 and C2,provides valuable insights into the clinical heterogeneity of hepatocellular carcinoma and its correlation with prognosis,tumor microenvironment characteris-tics,and immunotherapy response rates.The expression of GSDMC is decreased in hepatocellular carcinoma tissues and cells,and GSDMC inhibits the stemness of hepatocellular carcinoma cells.
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