A Pan-Cancer Analysis of SRD5A1, a Potential New Carcinogenic Indicator Related to Immune Infiltration and Prognosis of UCEC

Abstract Background: Steroid 5-Alpha-reductase type I (SRD5A1) converts testosterone to dihydrotestosterone and regulates sex hormone levels, which facilitates tumor incidence or progression. However, the molecular mechanism behind SRD5A1's role in pan-cancer remains unknown. Methods: RNA-seq data from TCGA and the Genotype-Tissue Expression (GTEx) database were used to examine SRD5A1 expression. String, HPA, GEPIA2, TIMER2, and cBioportal database were used to explore the protein and immune cell infiltration information of SRD5A1. The R package “ClusterProfiler” was used to conduct KEGG and GO enrichment analyses, and CancerSEA was used to investigate the functional heterogeneity of cancer cells. Results:SRD5A1 expression was differentially and higher predicted worse survival status in most tumor samples. Increased expression of SRD5A1 was detrimental to the clinical prognoses of cancer patients, especially UCEC. SRD5A1 expression was closely correlated with T cell infiltration and immune checkpoints. There were significant correlations between SRD5A1 expression and tumor mutation burden (TMB) or microsatellite instability (MSI)in several cancers. High SRD5A1 levels were associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that SRD5A1 participated in Transcription Androgen Receptor nuclear signaling and Metabolism. Finally, we validated pan-cancer SRD5A1 expression, and its impacts on immune infiltrate in UCEC.Conclusion:Our results suggest that SRD5A1 may contribute to the immune infiltration in the tumor microenvironment. SRD5A1 might synergize with other immune checkpoints serve as a carcinogenic indicator related to prognosis in pan-cancer, especially UCEC, and shed new light on therapeutics of cancers for clinicians.