Protein Kinase D1 (PRKD1) as a Diagnostic, Prognostic, and Immunomodulatory Biomarker in Human Cancers

Abstract

BACKGROUND AND AIM: Protein kinase D1 (PRKD1), a serine/threonine kinase, regulates cellular processes such as proliferation, apoptosis, migration, and immune responses. Depending on the tumor context, PRKD1 exhibits either oncogenic or tumor-suppressive functions. This study aimed to delineate the role of PRKD1 in cancer progression and assess its diagnostic and prognostic potential across multiple cancer types. MATERIALS AND METHODS: We analyzed PRKD1 expression using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases, and assessed its prognostic significance via the Kaplan-Meier plotter. Mutation profiles were examined using cBioPortal, while gene-gene and protein-protein interactions were evaluated through GeneMANIA and STRING, respectively. Pathway enrichment was performed using Enrichr. Findings were validated using three GEO datasets: GSE24152, GSE15641, and GSE110224. RESULTS: PRKD1 expression was significantly downregulated in bladder urothelial carcinoma (BLCA), kidney chromophobe (KICH), and rectum adenocarcinoma (READ) (all p < 0.001). Expression levels varied significantly with clinical parameters, including age, gender, race, and tumor stage. Immune infiltration analysis revealed significant associations between PRKD1 expression and immune cell subsets, namely, B cells, CD4⁺ T cells, macrophages, neutrophils, and dendritic cells in thyroid carcinoma (THCA), stomach adenocarcinoma (STAD), liver hepatocellular carcinoma (LIHC), and kidney renal clear cell carcinoma (KIRC). A notable inverse correlation was observed between PRKD1 and CD8⁺ T cell levels in THCA (p > 0.05). Survival analysis demonstrated that low PRKD1 expression correlated with improved prognosis in STAD, THCA, and LIHC, whereas high expression was favorable in KIRC (p = 0.001). Promoter methylation of PRKD1 was significantly increased in KICH and READ and decreased in BLCA (all p < 0.001), suggesting epigenetic regulation underlies its differential expression. CONCLUSION: PRKD1 serves as a potential diagnostic biomarker in BLCA, KICH, and READ, and as a prognostic indicator in STAD, THCA, LIHC, and KIRC. Its expression is modulated by epigenetic mechanisms and correlates with immune cell infiltration, underscoring its relevance in tumor immunobiology and potential as a therapeutic target.