Understanding the Role of Pyruvate Dehydrogenase Kinase 3 in Gynecological Cancers

OBJECTIVE: To investigate the role of pyruvate dehydrogenase kinase 3 (PDK3) in gynecological cancers through in silico analyses and in vitro experimental validation, and to assess its potential prognostic and therapeutic significance.

METHODS: • Analyzed gynecological cancer datasets from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases to evaluate PDK3 expression. • Performed KEGG pathway enrichment analysis to identify biological pathways associated with PDK3. • Kaplan-Meier survival analysis revealed cancer-type-specific associations between PDK3 expression and overall survival in breast, cervical, and endometrial cancer. • Assessed the impact of PDK3 expression on immune cell proportion and distribution in breast, cervical, and endometrial cancers. • Performed PDK3 knockdown experiments in SiHa cells to evaluate its effects on cell proliferation and growth.

RESULTS: • PDK3 was significantly upregulated in breast, cervical, and endometrial cancer samples compared with corresponding normal tissues. • KEGG pathway analysis showed significant enrichment of pathways related to cancer, viral carcinogenesis, and human papillomavirus (HPV) infection. • Elevated PDK3 expression was associated with poorer overall survival in breast and cervical cancer patients. • PDK3 upregulation influenced the proportion and distribution of immune cells in breast, cervical, and endometrial cancers. • Experimental knockdown of PDK3 significantly inhibited the proliferation and growth of SiHa cells.

CONCLUSION: PDK3 appears to function as a potential oncogene in gynecological cancers. Its overexpression is associated with tumor progression, altered immune cell infiltration, and reduced survival in certain gynecological cancers. Therefore, PDK3 may serve as a promising prognostic biomarker and therapeutic target in gynecological malignancies.