High Expression of SRD5A3 in Human Hepatocellular Carcinoma (HCC) Predicts Poor Prognosis: A Study Based on TCGA Data

Abstract Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Steroid 5 alpha-reductase 3 (SRD5A3) was reported to be up-regulated in many types of cancer. However, its expression and role in HCC remains to be elucidated. We aim to evaluate the significance of SRD5A3 expression in HCC by using analysis of a public dataset from The Cancer Genome Atlas (TCGA). Methods: The relationship between clinical pathologic features and SRD5A3 were analyzed with the Kolmogorov‐Smirnov test and the logistic regression. Cox regression and the Kaplan-Meier method were used to assess the clinicopathologic characteristics associated with overall survival (OS) in TCGA patients. In addition, GSEA was used to predict potential hallmarks associated with different expression of SRD5A3 on transcriptional sequences from TCGA database. Results: SRD5A3 was highly expressed in HCC tumor tissue compared to normal tissue. A total of 184 upregulated DEGs (differentially expressed genes) and 58 downregulated DEGs were identified between high expression and low expression of SRD5A3. Among them, 22 hub genes mainly belonging to the keratin and MUC family demonstrated by connectivity degree in the PPI network were screened out. Kaplan-Meier method showed that HCC patients in the high SRD5A3 expression group had poorer overall survival (OS, HR=2.26(1.58-3.24), p<0.001). In addition, cell cycle mitotic, cell cycle checkpoints, mitotic nuclear division, Q-glycan processing, protein O-linked glycosylation were differentially enriched in the high SRD5A3 expression phenotype pathway. In addition, SRD5A3 expression level has significant correlations with infiltrating levels of Th17 (R = -0.238, p < 0.001), Cytotoxic cells (R = -0.234, p < 0.001) and Th2 cells (R = 0.258, p < 0.001) in HCC. Conclusions: High expression of SRD5A3 was significantly correlated with poor prognosis in HCC patients. It may be a potential biomarker in HCC.