Comprehensive multi-omics analysis of CD36 in pan-cancers: Evaluating role in prognosis, immune microenvironment, and therapeutic response

Cluster of differentiation-36 (CD36) is involved in cellular adhesion, lipid metabolism, immunity, and inflammation. Multiple studies have enlightened the regulatory roles of CD36 in metabolic reprogramming, metastasis, chemoresistance, stemness, immune modulation, senescence, inflammation, and angiogenesis. However, its role in tumorigenesis is still unclear and context-dependent. We performed a comprehensive pan-cancer analysis of CD36 by using data from TCGA, integrating transcriptomic, proteomic, methylation, mutational, immune infiltration, immunotherapy, and drug sensitivity datasets. Expression patterns, clinical associations, prognostic potential, immune interactions, and therapeutic implications were systematically evaluated. We also evaluated CD36-related molecular pathways and immune signatures in cancer by a comprehensive GSEA analysis. We found that CD36 expression pattern is dysregulated in multiple cancer types, whereas higher expression correlated with poor prognosis in LGG, BRCA, CESC, and LAML. <i>CD3</i>6 mRNA showed inverse correlations with methylation levels. GSEA analysis revealed cancer-type-dependent association of CD36 with hallmark pathways, whereas multiple cancer types showed positive correlation with immune and inflammation-related pathways and negative correlation with cell cycle-related pathways. CD36 expression correlated with macrophage infiltration, immune regulators, and immunotherapy outcomes, including T-cell dysfunction and Immune checkpoint blockade (ICB) response. Moreover, drug sensitivity analyses revealed significant associations between CD36 and anticancer compound responses. This study provides a comprehensive and context-dependent landscape of CD36, establishing its oncogenic and immune-regulatory roles. Our findings highlight the potential of CD36 in prognosis, tumor microenvironment, and therapeutic sensitivity, while experimental validation is required to prove therapeutic relevance in cancer therapy and immunotherapy.