Abstract
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.
Highlights
Renal Cell Carcinoma is the third most common cancer of the genitourinary tract [1] and its incidence is increasing in the United States [2]
A complex metabolic derangement characterized by skeletal muscle and fat loss develops in a significant number of patients with clear cell variant of Renal Cell Carcinoma (ccRCC)
There was no significant difference in tumor grade, American Joint Committee on Cancer (AJCC) stage, or tumor laterality between men and women
Summary
Renal Cell Carcinoma is the third most common cancer of the genitourinary tract [1] and its incidence is increasing in the United States [2]. Represents over 80% of all histologic subtypes of renal cancer [3], and is frequently associated with the development cachexia symptoms [4,5,6]. Cancers 2020, 12, 1605 have shown that development of cachexia is associated with a three-fold increased rate of disease recurrence and a four-fold increased risk of disease specific death in patients with ccRCC [7]. It has been established that the development of cachexia symptoms is associated with a decreased overall survival [3,6,12,13], and poor outcomes following surgery or targeted therapy for ccRCC [14,15,16,17]. Low muscle mass has been shown to be a significant predictor of sorafenib toxicity in patients with metastatic renal carcinoma [18]
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