In vitro analysis of PI3K pathway activation genes for exploring novel biomarkers and therapeutic targets in clear cell renal carcinoma

Objectives: The regulation of various cellular functions such as growth, proliferation, metabolism, and angiogenesis, is dependent on the PI3K pathway. Recent evidence has indicated that kidney renal clear cell carcinoma (KIRC) can be triggered by the deregulation of this pathway. The objective of this research was to investigate 25 genes associated with activation of the PI3K pathway in KIRC and control samples to identify four hub genes that might serve as novel molecular biomarkers and therapeutic targets for treating KIRC.

Methods: Multi-omics in silico and in vitro analysis was employed to find hub genes related to the PI3K pathway that may be biomarkers and therapeutic targets for KIRC.

Results: Using STRING software, a protein-protein interaction (PPI) network of 25 PI3K pathway-related genes was developed. Based on the degree scoring method, the top four hub genes were identified using Cytoscape's Cytohubba plug-in. TCGA datasets, KIRC (786-O and A-498), and normal (HK2) cells were used to validate the expression of hub genes. Additionally, further bioinformatic analyses were performed to investigate the mechanisms by which hub genes are involved in the development of KIRC. Out of a total of 25 PI3K pathway-related genes, we developed and validated a diagnostic and prognostic model based on the up-regulation of TP53 (tumor protein 53) and CCND1 (Cyclin D1) and the down-regulation of PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), and GSK3B (Glycogen synthase kinase-3 beta) hub genes. The hub genes included in our model may be a novel therapeutic target for KIRC treatment. Additionally, associations between hub genes and infiltration of immune cells can enhance comprehension of immunotherapy for KIRC.

Conclusion: We have created a new diagnostic and prognostic model for KIRC patients that uses PI3K pathway-related hub genes (TP53, PTEN, CCND1, and GSK3B). Nevertheless, further experimental studies are required to ascertain the efficacy of our model.