Abstract

BackgroundPrediction of outcomes in patients with renal cell carcinoma (RCC) is crucial for clinical decision-making. The limited accuracy of conventional prognostic factors such as stage and grade may be increased by the use of biomarkers. ObjectiveTo evaluate the association of serum adiponectin and leptin and polymorphisms in the leptin and leptin receptor genes with RCC histopathology and prognosis. Design, setting, and participantsAdiponectin and leptin levels were measured in preoperative serum samples from 131 consecutive patients with sporadic unilateral RCC. The polymorphisms G–2548A (rs7799039) in the leptin gene (LEP) and Gln223Arg (Q223R, A668G, rs1137101) in the leptin receptor gene (LEPR) were genotyped in 233 patients. Outcome measurements and statistical analysisMultivariable associations with RCC-specific survival were analyzed using Cox models. Results and limitationsMedian preoperative serum adiponectin was 15.8μg/ml (interquartile range 10.0–23.1). Adiponectin was lower in patients with distant metastases (p=0.017) or histologic tumor necrosis (p=0.015). On multivariable analysis adjusted for the effects of variables in the Karakiewicz nomogram, each 1-μg/ml increase in adiponectin was associated with a 8% decrease in the hazard of death from RCC (hazard ratio 0.92, 95% confidence interval 0.86–0.98; p=0.007). The discrimination of the Karakiewicz nomogram increased by 0.6% on inclusion of adiponectin. Leptin levels, LEP G–2548A and LEPR Q223R were not associated with either RCC pathology or outcomes. Limitations include the retrospective study design, the low numbers of patients, and a lack of standardized follow-up. ConclusionsThis study suggests that lower preoperative serum adiponectin is associated with features of biologically aggressive RCC, metastasis, and survival. Patient summaryWe assessed the relationship between outcomes and blood levels of adiponectin and leptin and genetic changes in leptin and leptin receptor genes. We found that patients with lower adiponectin levels have more aggressive tumors and poorer survival.

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