Presentation Authors: Wen-Hao Xu, Yuan-Yuan Qu*, Wang Jun, Fang-Ning Wan, Hong-Kai Wang, Jian-Yuan Zhao, Hai-Lang Zhang, Dingwei Ye, Shanghai, China, People's Republic of
Introduction: 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
Methods: Real-Time quantitative PCR 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 Ï‡2-test in a contingency table. Differential expression of CD36 in normal tissue versus tumor tissues was screened in The Cancer Genome Atlas (TCGA) database. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by magnetic resonance imaging (MRI) and identified at the level of the umbilicus. Pearsonâ€™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 benifits between discrete levels.Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from The Cancer Genome Atlas (TCGA) database.
Results: In the current study, we demonstrated that CD36 mRNA was highly expressed in ccRCC compared with normal tissues. In addition, CD36 mRNA expression was found significantly increased in patients with advanced TNM stage (p=0.003, p < 0.001, p < 0.001), and high VAT% (p=0.004). Pearsonâ€™s correlation coefficient indicated 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). Meanwhile, median PFS was 60 months and OS was 99 months. Furthermore, 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 whose MRI scans were available, VAT was significantly correlated with poor PFS and OS, with hazard ratios 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-Î²) signaling pathways.
Conclusions: 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.
Source of Funding: This work is supported by Grants from the National Natural Science Foundation of China (Nos. 81202004, 81802525, 81722021, 81771627, 81471454), Shanghai Natural Science Foundation of China (No. 16ZR1406400), Science and Technology Municipal Commission of