HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance.

Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance.