PDK4 Constitutes a Novel Prognostic Biomarker and Therapeutic Target in Gastric Cancer

Abstract

Gastric cancer (GC) is one of the most prevalent and deadly malignancies worldwide. We aimed to assess the functional role and clinical significance of pyruvate dehydrogenase kinase (PDK) in GC and explored the underlying mechanisms. The bioinformatics method was used to investigate the expression of PDKs in GC, the effect on clinical outcomes, enriched pathways, interactive network, and the correlation between PDK4 and immune infiltration. Next, PDK expression in the GC cells and tissues were verified by qRT-PCR and western blotting. A Cell Counting Kit-8 (CCK8), colony-formation, Flow cytometry, Transwell and wound healing assays were carried out to evaluate the influence of PDK4 on cell proliferation, invasion and migration. Among PDKs, PDK4 expression was aberrant in GC and identified as an independent prognostic factor. GO analysis, GSEA, and PPI showed that PDK4 expression may regulate cell adhesion, metal ion transport, synaptic activity, and cancer cell metabolism in GC. Analyses of immune infiltration showed that PDK4 correlated with the abundant expression of various immunocytes. Finally, we verified that upregulation of PDK4 expression enhanced the ability of GC cells to proliferate, migrate, and invade. In conclusion, PDK4 was identified as a potential candidate diagnostic biomarker and therapeutic target for GC patients.

Keywords

• gastric cancer
• PDK family
• biomarker
• cancer metabolism
• prognostic model
• tumor growth