• Yuming Lu, Ziwei Liu, Yu Zheng, Xuesong Liu, XiaoQin Liu, Nanguan Chen, Kai Mao, and Weida Lin.
• Department of Biostatistics, College of Science, City University of Hong Kong, Hong Kong, China.
• Ann. Med. 2024 Dec 1; 56 (1): 24084632408463.

IntroductionThis study combined the bioinformatics and in vitro experiment-related technologies to analyze the impact of steroid 5 alpha-reductase 3 (SRD5A3) on the prognosis and immune microenvironment of Liver Hepatocellular Carcinoma (LIHC).MethodGene expression and clinical data were obtained from public databases. The prognosis was evaluated using survival, multifactor Cox, enrichment, and mutation analyses. This was then verified through in vitro experiments.ResultsThe expression level of SRD5A3 in LIHC tissues was significantly higher than that in the adjacent tissues. Kaplan-Meier survival analysis showed that high SRD5A3 expression was associated with poor overall survival (OS) and short progression-free survival in patients with LIHC. Multivariate Cox regression analysis revealed that positive SRD5A3 expression was an independent risk factor for OS in patients with LIHC. Expression of SRD5A3 was negatively correlated with immune cell infiltration of CD4+ T, CD8+ T, and B cells. GO and KEGG enrichment analyses showed that SRD5A3 was significantly enriched in signaling- and tumor metastasis-related pathways. Nomogram and calibration curve showed that the predicted performance of the model was consistent with the actual results. In vitro results confirmed that SRD5A3 knockdown inhibited the migration, invasion, and proliferation of LIHC cells.ConclusionsSRD5A3 is actively expressed in LIHC, and positive expression of SRD5A3 is an independent risk factor for different prognoses in patients with LIHC. SRD5A3 can promote the proliferation, migration, and invasion of liver cancer cells and is related to short immune infiltration in patients with LIHC.

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