Treg-Related Genes Representing a Potential Shared Biological Mechanism Between Clear Cell Renal Carcinoma and Obesity.

Objective: To determine the potential shared biological mechanism between obesity and clear cell renal carcinoma (ccRCC).

Study Design: Observational study. Place and Duration of the Study: Department of Urology, Lishui People's Hospital, Lishui City, China, from December 2022 to March 2023.

Methodology: The test and validation cohorts were selected from the GEO database. WGCNA and PPI networks were applied to identify shared hub genes. GO/KEGG, GSEA, and ROC curve analyses were applied to explore the potential underlying mechanisms and diagnostic power. Logistic regression was used to select genes to construct the signature. The risk score and various immune-related analyses were performed to assess the clinical and immune performance of the signature. The CellMiner platform was used to screen potential FDA-approved drugs.

Results: PTPRC, TYROBP, ITGB2, CD86, and ITGAM were defined as shared hub genes with good diagnostic power for obesity and ccRCC. Eight immune cells exhibited a positive correlation with the hub genes, while two immune cells showed negative associations. MDSCs and Tregs had the strongest positive associations with the hub genes. The Treg-related pathway exhibited predominant enrichment. The TYROBP, ITGB2, and CD86 genes were selected to construct an immune signature that has good clinical and immune performance. Six FDA-approved drugs were screened.

Conclusion: Five Treg-related genes were identified as shared hub genes in obese patients and ccRCC patients. A signature was constructed to describe the immune features of ccRCC.

Key Words: Treg-related genes, Shared biological mechanism, Immune signature, Obesity, Clear cell renal carcinoma (ccRCC).