The Molecular Mechanism of CD36 in Regulating Cholesterol Metabolism Reprogramming to Drive the Pathogenesis of Diffuse Large B-Cell Lymphoma Cells
Authors: Cheng Wei , Zhou Lili , Luo Qingqing , Luo Yi , Yu Li 
Published: December 2024

Introduction: Diffuse large B-cell lymphoma (DLBCL) represents one of the most prevalent adult lymphomas, characterized by significant clinical heterogeneity and prognosis. The precise relationship between cholesterol metabolism and DLBCL remains elusive. This research endeavors to delineate the molecular mechanisms through which CD36 orchestrates cholesterol metabolic reprogramming to sustain lymphoma viability.
Methods: Patients with DLBCL and healthy controls treated at the Second Affiliated Hospital of Nanchang University from January 2010 to October 2020 were selected for this study. Clinical data were analyzed to assess the correlation between cholesterol metabolism indicators and prognosis. Different invasive DLBCL cell lines and normal lymphocyte cell lines were screened to detect the levels of CD36 and cholesterol metabolism indicators, analyze their correlation, and their relationship with tumor cell survival. Finally, the mechanism by which CD36 regulates cholesterol metabolism to sustain the survival of DLBCL cell lines was explored by interfering with the expression of CD36 and cholesterol.
Results: In a cohort of 160 DLBCL patients treated at the Second Affiliated Hospital of Nanchang University and a group of healthy controls, a comprehensive analysis of lipid profiles revealed significantly lower levels of APOA1 in the DLBCL cohort. This study further elucidated a positive correlation between APOA1 levels and both overall survival (OS) and progression-free survival (PFS) in DLBCL patients, firmly establishing APOA1 as a critical, independent prognostic marker for OS and PFS. Immunohistochemistry confirmed the elevated expression of CD36, with higher CD36 expression levels correlating with poorer patient prognosis. Moreover, a parallel relationship between CD36 expression and cholesterol levels was identified. In vitro experiments with DLBCL cell lines revealed a differential expression pattern of CD36, where expression levels were inversely and significantly correlated with patient prognosis. Further investigation of cholesterol metabolism-related biomarkers showed that lymphoma cell lines WSU-DLCL2 and OCL-LY3, exhibited heightened expression of CD36, when compared to normal lymphocyte cell line GM12878. This upregulation was accompanied by an increase in the expression of cholesterol synthesis elements SREBP2, and rate-limiting enzymes HMGCR and SQLE, alongside a decrease in the expression of the cholesterol efflux gene ABCG1. These findings suggest an intricate interplay between increased cholesterol synthesis and reduced cholesterol efflux. Remarkably, the silencing of CD36 expression resulted in a reduction in cholesterol synthesis and a notable increase in cell apoptosis.
Conclusion: This research illuminates the existence of cholesterol metabolic reprogramming in DLBCL patients, where CD36 plays a pivotal role in sustaining tumor cell survival through the regulation of cholesterol metabolic reprogramming. Our work offers a novel perspective on the pathogenesis of DLBCL, highlighting potential therapeutic targets for its treatment.