Objective  To investigate the expression of activator of heat shock 90 kDa protein ATPase homolog 1 (AHSA1) in hepatocellular carcinoma (HCC) and analyze the relationship between AHSA1 expression level and prognosis.

  Methods  HCCDB, GEPIA and Oncomine databases were used to analyze the expression of AHSA1 mRNA in HCC and normal liver tissues. HCC RNA-seq expression and clinical information were downloaded from the Cancer Genome Atlas (TCGA), and univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots were used to evaluate the value of AHSA1 in predicting the prognosis of liver cancer. R software was used to construct the nomogram based on the expression level of AHSA1, and the calibration curve was plotted to evaluate the consistency between the actual survival and the predicted survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) gene set enrichment analyses were perform to reveal tumor-associated biological processes related to AHSA1. The TIMER2.0 and GFPIA database were used to evaluate the correlation between AHSAl and tumor immune infiltration in HCC. Small molecule targeted drugs acting on AHSA1 were screened by CMAP.

  Results  The expression level of AHSA1 in HCC tissues was significantly higher than that in normal tissues (P < 0.01). High expression of AHSA1 was associated with the poor prognosis of HCC (P < 0.05), and was an independent factor affecting overall survival (OS) (HR=1.970, P < 0.001). The nomogram showed that AHSA1 gene expression was correlated with the risk of HCC, and the area under the curve (AUC) of predicting OS at 1 year, 3 and 5 years were 0.721, 0.711 and 0.725, respectively. The calibration chart showed that the predicted survival rate curve was in good agreement with the actual survival rate curve. GO and KEGG enrichment analysis showed that AHSAl was able to promote tumor progression by mediating neutrophil activation and participating in biological processes such as glycolysis and gluconeogenesis. The expression level of AHSA1 mRNA was associated with the degrees of immune infiltration by B cells, CD4⁺ T cells, regulatory T cells, macrophages, neutrophils and dendritic cells (P < 0.05). Etacrynic acid and blebbistatin might be the small molecule targeted drugs that can reverse the expression of AHSA1.

  Conclusion  AHSA1 mRNA may be a potential oncogene in HCC, the high expression of AHSA1 mRNA may promote the immune infiltration of HCC tissues, and is associated with poor prognosis of HCC patients.