Abstract 6218: Impact of body composition on tumor proteomics and survival outcomes in clear cell renal cell carcinoma

Background: The prognosis of clear cell renal cell carcinoma (ccRCC) is affected by a complex interaction of tumor characteristics and patient factors. This study investigates the association between body composition components with survival and tumor proteomics in patients with ccRCC. Methods: We identified 178 patients from the TCGA-Kidney Renal Clear Cell Carcinoma project with CT images and tumor proteomic data (233 proteins). CT images corresponding to the 3rd lumbar vertebrae were assessed using Slice-O-Matic software for adipose and skeletal muscle tissue areas. The Contal and O’Quigley's method was used to obtain the cutoffs for categorizing patients into high or low groups of adiposity and muscle based on survival. Patients were further classified into four body composition types: (1) High Muscle/Low Adiposity, (2) High Muscle/High Adiposity, (3) Low Muscle/Low Adiposity, and (4) Low Muscle/High Adiposity. Linear regression was used to assess the associations for protein expression. Cox’s hazard models were used for survival analysis. All models were adjusted for age, stage, gender, race, and ethnicity. Results: There was no significant difference in survival based on muscle quantity alone. However, patients with low adiposity had worse survival than those with high adiposity (hazard ratio [HR] = 2.7; 95% CI= 1.2, 5.8). For body composition types, compared to the high muscle/high adiposity group, which had the best survival, the low muscle/low adiposity group had a significantly worse survival (HR = 3.5; 95% CI = 1.5, 8.2). Different muscle/adiposity combinations exhibited distinct protein expression patterns (all false-discovery-rate p-value ≥0.2). Low muscle/low adiposity exhibited a pattern of increased cell survival and proliferation with decreased tumor suppression, while low muscle/high adiposity exhibited increased cell motility and migration. Body composition also significantly affected survival based on expression levels of PREX1 and JAK2. Low muscle/high adiposity (vs. high muscle/high adiposity) was associated with increased mortality among patients with high PREX1 expression (HR =6.72; 95% CI = 1.88, 24.03) but not among those with low PREX1 expression (HR=1.07; 95% = 0.28, 3.99); p-value for interaction = 0.048). Also, the body composition type was associated with increased mortality among patients with high JAK2 expression (HR= 7.50; 95% CI = 1.37, 41.07) but not among those with low JAK2 expression (HR = 1.09; 95% CI= 0.35-3.39; p-value for interaction = 0.065). Conclusion: Body composition in patients with ccRCC is associated with overall survival and with several tumor protein expressions. The mortality risk can vary based on tumor protein markers. These findings warrant further validation as they highlight the potential utilization of body composition as a prognostic biomarker and therapeutic target. Citation Format: Cuthbert M. Mahenge, Rand T. Akasheh, Xuan Nguyen, Ting-Yuan D. Cheng. Impact of body composition on tumor proteomics and survival outcomes in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6218.