Molecular Remodeling of Peritumoral Tissue in Clear Cell Renal Cell Carcinoma: Insights into Inflammaging and Prognostic Markers

Background/Objectives: Renal cell carcinoma (RCC) is a common and often asymptomatic malignancy with limited treatment options for advanced stages. Chronic inflammation and cellular senescence-collectively termed "inflammaging"-are emerging as key contributors to tumor progression. This study aimed to investigate the expression of inflammaging-related markers in RCC tissues, focusing on the role of PTX3, IL-6, and senescence-associated proteins in the tumor microenvironment. Methods: A retrospective cohort of 57 patients with clear cell RCC who underwent nephrectomy was analyzed. Formalin-fixed paraffin-embedded samples from tumor, peritumoral, and normal renal tissues were examined using confocal immunofluorescence microscopy to assess PTX3, IL-6, p21, and p16 expression. Senescence-associated β-galactosidase staining was performed to identify senescent cells. Serum IL-6 levels were measured by ELISA, and survival analysis was conducted using Kaplan-Meier curves and Cox regression analysis. Results: PTX3 and IL-6 were significantly upregulated in both peritumoral and tumor tissues compared to normal kidney samples (p p p p p Conclusions: Our findings suggest that peritumoral tissue in RCC exhibits a senescent and proinflammatory phenotype that may support tumor progression. PTX3 and IL-6 are potential biomarkers of disease severity and prognosis. Targeting inflammaging pathways could offer new therapeutic strategies for RCC, particularly in aggressive disease forms.