Immunological perspective on the malignant progression of renal clear cell carcinoma

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common malignancy affecting the kidneys, accounting for approximately 75% of all kidney tumors. Recently, the impact of immune response, immunotherapy, and immune-related genes (IRGs) on tumor development has received much attention. This study sought to establish a reliable immunological signature and further explore whether this signature has prognostic significance in ccRCC patients. METHODS: Differentially expressed IRGs in 611 patients with diagnosis of ccRCC from The Cancer Genome Atlas (TCGA) were analyzed along with the corresponding survival time and disease clinical data. Survival analysis, selection operator Cox analysis, and minimum absolute shrinkage were applied to establish an IRG prognostic signature (IRGPS). The expression levels of relevant genes were detected by real-time quantitative PCR. A Nomogram was used to explore the possible impact of the IRGPS on the immune system, prognosis, and metastasis, and the associated mechanisms were explored through functional enrichment analysis. RESULTS: An IRGPS was established based on eight prognostic IRGs and was found to be closely associated with immune levels, metastasis, and prognosis. The IRGPS was determined to be a valid predictor of the efficacy of immune checkpoint inhibitors (ICIs). Three Nomograms based on the IRGPS and other clinical features were developed and could effectively predict prognosis, distant metastasis, and lymph node metastasis in patients with ccRCC. CONCLUSIONS: The IRGPS constructed in this study serves as a tool for assessing immune status, developing individualized treatment regimens, and predicting prognosis in patients with ccRCC.