Objective: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR gene expression analysis was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test in a contingency table. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by magnetic resonance imaging (MRI) and identified at the level of the umbilicus. Pearson's correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Partial likelihood test from univariate and multivariate Cox regression analysis were developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels. Results: In the current study, CD36 mRNA was demonstrated highly expressed in ccRCC compared with normal tissues. In addition, CD36 mRNA expression was significantly increased in patients with advanced TNM stage (p=0.003, p<0.001, p<0.001), and high VAT% (p=0.004). Pearson's correlation coefficient indicated that CD36 amplification positively correlated with BMI (r=0.117, p=0.025), VAT% (r=0.465, p<0.001), while negatively associated with SAT (r=-0.296, p=0.002). Median PFS was 60 months and OS was 99 months. Meanwhile, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with hazard ratios [HR; 95% confidence interval (CI)] of 4.873 (3.300-7.196, p<0.001) and 4.610 (2.956-7.189, p<0.001). In 104 cases with available MRI scans, VAT was significantly correlated with poor PFS and OS, with HR of 2.556 (1.036-6.310, p<0.042) and 3.291 (1.034-10.477, p<0.044). A total of 100 significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, UV response, angiogenesis and transforming growth factor beta (TGF-β) signaling pathways. Conclusion: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.
Journal of Cancer. 2019 Jul 25*** epublish ***
Wen-Hao Xu, Yuan-Yuan Qu, Jun Wang, Hong-Kai Wang, Fang-Ning Wan, Jian-Yuan Zhao, Hai-Liang Zhang, Ding-Wei Ye
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032., The Obstetrics & Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences and Collaborative Innovation Center of Genetics & Development, Fudan University, Shanghai 200032, P.R. China.