Integrative analysis reveals PRKCB and SRD5A2 as potential immune-associated biomarkers in prostate cancer targeted by traditional Chinese medicine.

BACKGROUND: Prostate cancer (PCa) is a major malignant tumor that significantly threatens male health, in which various immune pathways are critically involved in its pathogenesis. This study aims to elucidate the immunomodulatory mechanisms of active constituents from 11 traditional Chinese medicines in PCa. METHODS: By eliminating batch effects between the GSE69223 and GSE246282 datasets, we integrated weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, protein-protein interaction (PPI) network analysis, and the CIBERSORT algorithm to identify the active components of traditional Chinese medicines and potential hub immunological biomarkers associated with immune cells. Functional enrichment analyses were conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Variation Analysis (GSVA). Molecular docking was employed to evaluate the interactions between active compounds and potential immunotherapeutic targets. In addition, immunohistochemistry was conducted to validate the protein expression of key targets in clinical prostate cancer tissues. RESULTS: Among the 2,610 differentially expressed genes (DEGs) identified, PRKCB and SRD5A2 emerged as key hub genes. Notably, both genes exhibited significant correlations with immune cell infiltration and showed strong binding affinities to the active compounds kaempferol, isorhamnetin, and rhamnazin. Furthermore, functional enrichment analyses revealed the intricate involvement of the DEGs, hub genes, and candidate biomarkers in pathways closely related to immunity and prostate cancer. Finally, the expression levels of PRKCB and SRD5A2 were validated in prostate cancer and adjacent normal tissues using clinical samples. CONCLUSION: PRKCB and SRD5A2 were identified as potential immunological biomarkers and immunotherapeutic targets associated with immune cell infiltration in PCa, both of which were significantly downregulated in PCa tissues. Moreover, kaempferol, isorhamnetin, and rhamnazin exhibited potential immunomodulatory effects in PCa by regulating the expression of PRKCB and SRD5A2.