The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma

Clear cell renal carcinoma (ccRCC) is frequently associated with cachexia which is itself associated with decreased survival and quality of life. We examined relationships among body phenotype, tumor gene expression, and survival. Demographic, clinical, computed tomography (CT) scans and tumor RNASeq for 217 ccRCC patients were acquired from the Cancer Imaging Archive and The Cancer Genome Atlas (TCGA). Skeletal muscle and fat masses measured from CT scans and tumor cytokine gene expression were compared with survival by univariate and multivariate analysis. Patients in the lowest skeletal muscle mass (SKM) quartile had significantly shorter overall survival versus the top three SKM quartiles. Patients who fell into the lowest quartiles for visceral adipose mass (VAT) and subcutaneous adipose mass (SCAT) also demonstrated significantly shorter overall survival. Multiple tumor cytokines correlated with mortality, most strongly interleukin-6 (IL-6); high IL-6 expression was associated with significantly decreased survival. The combination of low SKM/high IL-6 was associated with significantly lower overall survival compared to high SKM/low IL-6 expression (26.1 months vs. not reached;p< 0.001) and an increased risk of mortality (HR = 5.95; 95% CI = 2.86-12.38). In conclusion, tumor cytokine expression, body composition, and survival are closely related, with low SKM/high IL-6 expression portending worse prognosis in ccRCC.