Association between visceral adiposity and DDX11 as a predictor of aggressiveness of small clear-cell renal-cell carcinoma: a prospective clinical trial.

BACKGROUND: Visceral fat produces several hormones and cytokines associated with carcinogenesis and tumor progression. Herein, we investigated the association between visceral adiposity and target-gene mRNA expression in patients with localized small clear-cell renal-cell carcinoma (ccRCC). METHODS: We included 200 patients with localized clinical T1a stage ccRCC who had undergone nephrectomy from November 2018 to November 2020 in a prospective clinical trial (NCT03694912). Visceral, subcutaneous, and total adipose tissue in these patients was measured via preoperative computerized tomography of the mid-third lumbar vertebra region. We then examined the association between adiposity and the mRNA levels of PBRM1, BAP1, SETD2, KDM5C, FOXC2, CLIP4, AQP1, DDX11, BAIAP2L1, and TMEM38B in matched frozen tumor tissues and plasma samples. RESULTS: Upon the stratification of patients into quartiles according to their relative visceral adiposity, high visceral adiposity was found to be significantly associated with low ISUP grade (P = 0.004). Multivariate logistic regression analysis revealed a significant association between frozen tissue DDX11 expression and high visceral adiposity (OR 0.676, 95% CI 0.587-0.779, P < 0.001). Moreover, frozen tissue DDX11 expression was significantly associated with high ISUP grade (OR 1.556, 95% CI 1.223-1.981, P < 0.001). The frozen tissue mRNA expression of DDX11 was identified as a biomarker for visceral adiposity and cancer aggressiveness. CONCLUSIONS: The results obtained herein will aid in inferring the aggressiveness of small ccRCCs, represented by ISUP nuclear grade, in clinical practice. Our findings indicated that DDX11 and visceral fat play active roles in small ccRCC. These roles should be examined in future studies for the possible use of DDX11 and visceral fat as prognostic biomarkers in the treatment of patients with ccRCC. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03694912 , Registered 3 October 2018.