The Associations Of HMGA1 With Prognosis And Immune Factors In Hepatocellular Carcinoma Based On Bioinformatics

ObjectiveThe aim of this study was to comprehensively identify differences in HMGA1 expression between HCC and normal liver tissues by bioinformatics analysis using high-throughput sequencing data from hepatocellular carcinoma(HCC)in the public Cancer Genome Atlas Database(TCGA)and the Integrated Gene Expression Database(GEO).At the same time,the relationship between HMGA1 and tumor immune microenvironment,especially immune cells and immunosuppressive factors,was analyzed,so as to provide a new direction for the immunological study of HMGA1 in HCC.MethodsTCGA,GEO and HPA databases were used to analyze whether there were differences in the expression of HMGA1 between HCC and normal liver tissues.Kaplan-Meier(K-M)survival analysis showed the correlation between HMGA1 high expression and different clinicopathological factors and clinical prognosis.Univariate and multivariate cox analysis were used to screen prognostic factors related to HCC clinical outcomes.The possible types of changes in the HMGA1 genome were analyzed from the c Bio Portal database.Immune cells and immune regulatory factors associated with HMGA1 in HCC were screened based on GSCA and TISIDB databases.Finally,the signaling pathway that HMGA1 may be involved in HCC was determined by gene enrichment analysis.Results1.The expression of HMGA1 is different between HCC and normal liver tissue,that is,HMGA1 is highly expressed in HCC.Overall survival(OS),progression-free survival(PFS),relapse-free survival(RFS)and disease-specific survival(DSS)are all lower in HMGA1 highly expressed HCC patients.Kaplan-Meier(K-M)survival analysis showed that high expression of HMGA1 could be correlated with low OS and low PFS of all clinical factors.2.Univariate and multivariate analysis showed that the primary tumor and the high expression of HMGA1 could be independent predictors of clinical prognosis in HCC patients.3.The amplification of HMGA1 genome can lead to the increase of its expression level,and the increase of HMGA1 expression in HCC is mainly related to the decrease of DNA methylation level.4.The expression of HMGA1 is negatively correlated with the invasion of HCC neutrogranulocyte and Th17 cells,and the expression of HMGA1 is correlated with eight immunosuppressive factors including CSF-1R,CTLA-4,HAVCR2,LGALS9,PDCD1,TGF-β1,TIGIT and VTCN1.5.HMGA1 is involved in the "cell cycle","polysaccharide biosynthesis","nucleotide excision repair","meiosis","other glycan degradation","purine metabolism","pyrimidine metabolism","RNA degradation","spliceosome" and "ubiquitin-mediated proteolysis" pathways in HCC.ConclusionsThese findings demonstrate that HMGA1 can be a therapeutic target and a potential biomarker to predict the prognosis of patients with HCC,that is,patients with high expression of HMGA1 have worse clinical prognosis.HMGA1 may affect the progression of HCC by suppressing the immune function of these patients.