Can expression of CD36 be a metabolic marker of survival in muscle invasive urothelial carcinoma of the bladder?

Abstract

Background: There is continued interest in cancer metabolism due to its potential application in targeted cancer therapies. One of the promising lines of research is concerned with the CD36 protein which is involved in numerous metabolic processes. The role of CD36 in the regulation of angiogenesis and transportation of fatty acids into the cell was demonstrated, both of which are implicated in tumor development. However, the prognostic value of CD36 in urinary bladder cancer (UBC) has not been previously evaluated. The aim of this study was to assess the relation between CD36 expression in tumor cells and survival of patients with pT2-pT4 UBC. Materials and methods: 96 patients with stage pT2-pT4 UBC who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Archival paraffin blocks which were the most representative of tumor were selected based on H&E stained samples. Immunostaining was performed with a recombinant monoclonal rabbit anti-CD36 antibody (EPR6573, abcam). In each sample the intensity of CD36 expression was assessed on a binary scale as either high or low. Moreover, the extent of CD36 expression within the tumors was assessed as low in tumors with fewer than 30% of TCs expressing CD36 and high in tumors with more than 30% of the tumor cells expressing CD36. CD36 expression and the probability of survival were analyzed with Kaplan–Meier curves. Results: We observed an over two-fold decrease in 5-year survival of patients with high expression of CD36 compared to patients with low expression (p=0.004). Similarly, 2-year survival of patients with more than 30% of the tumor cells expressing CD36 was almost two-fold lower compared to patients with the extent of CD36 expression below 30% (p=0.028). Conclusions: The expression of CD36 in tumor cells allows for the stratification of survival in patients with UBC. The intensity and extent of CD36 expression may be considered as new prognostic factors which describe the metabolic status of cancer cells and their resulting malignant potential. Further research leading to the development of a model of metabolic tumor progression that incorporates CD36 expression could open new therapeutic opportunities for UBC patients.