ITPKA as a biomarker for proliferation, migration and metastasis in renal clear cell carcinoma

Inositol-Trisphosphate3-Kinase A (ITPKA), a phosphorylated kinase that acts primarily on cellular metabolism, is highly expressed in renal clear cell carcinoma (ccRCC) and is associated with tumor progression and prognosis, but the action mechanism of ITPKA in renal cell carcinoma is not yet fully understood. The differential expression pattern of ITPKA was investigated using Cancer Genome Atlas (TCGA) and GEPIA2 databases. The expression of ITPKA in ccRCC patients was further verified by immunohistochemical (IHC) examination of 20 clinicopathologic specimens. A protein-protein interaction (PPI) network was established to include ITPKA and differentially expressed genes. The role of ITPKA in the PPAR pathway was predicted by functional enrichment analysis. Our results showed that ITPKA was overexpressed in ccRCC, and the higher the expression, the worse the clinical outcomes such as TNM staging and pathological grading. Immune infiltration analysis suggested a potential link between ITPKA expression and immune infiltration. In addition, patients with high ITPKA expression had worse survival compared with patients with low expression. Finally, to validate our earlier studies, we performed cellular functional tests and protein imprinting assays on ccRCC cell line 786-O. The experimental results showed that ITPKA knockdown significantly reduced the invasion and migration rates of renal cell carcinoma tumor cells, while PPAR pathway activity was also significantly inhibited. Overall, our study revealed that ITPKA is a promising biomarker with prognostic potential in ccRCC. Its key regulatory role in the PPAR signaling pathway provides research value and lays the foundation for future targeted therapy research.