Prognostic and immunological role of CD36: A pan-cancer analysis

Abstract

CD36 plays a critical role in lipid metabolism, which is closely associated with human immunity. However, the role of CD36 in cancer remains unclear. We performed a pan-cancer analysis to elucidate the potential role of CD36 in cancer by investigating its prognostic value and current predictors for the efficacy of immune checkpoint inhibitors (ICIs) in multiple cancer types. CD36 expression in cancer cell lines, tumor tissue, and their adjacent normal tissues displayed heterogeneity among different cancers. Immunohistochemistry was used to detect CD36 expression and confirmed the results. CD36 expression significantly affects prognosis in the six cancer types. High CD36 expression was marginally associated with poorer prognosis in four of them and improved prognosis in the remaining two types. CD36 expression was significantly correlated with the 6 immune infiltrates in most cancer types. In addition, CD36 gene expression was positively correlated with Stromal score, Immune score, and ESTIMATE score. A total of 47 immune checkpoint genes were collected and their relationship with CD36 expression was analyzed. CD36 expression was significantly associated with multiple stimulatory and inhibitory checkpoint molecules with a disease-specific pattern. As to the genes reported to positively relate to the efficacy of ICIs, CD36 expression was positively correlated with most of them but negatively associated with a small proportion of cancer type-specific patterns. Concerning the genes negatively related to the efficacy of ICIs, CD36 expression was positively correlated with NRP1 and TNFSF15 in multiple cancers. CD36 expression was negatively correlated with tumor neoantigen burden in most cancer types. However, CD36 expression was negatively correlated with tumor mutation burden in most cancer types. The correlation between CD36 expression and the four methyltransferases was also significant in multiple cancers, but also with a cancer type-specific pattern. In summary, the current study found CD36 expression and its prognostic value in multiple cancer types. In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs. The practical application value of CD36 is disease specific.

Mitochondrial RNA modifications shape metabolic plasticity in metastasis

“…Upregulation of CD36 enhances the uptake of fatty acids for lipid homeostasis but can also fuel mitochondrial respiration under stress conditions 31 . CD36 expression correlates with poor patient survival in various types of cancer 32 , 33 , and when expressed together with CD44 initiates metastasis 18 . We show that the CD44- and CD36-expressing tumour cells only efficiently metastasize when using mitochondria as an energy source.…”

Protein Ligands in the Secretome of CD36+ Fibroblasts Induce Growth Suppression in a Subset of Breast Cancer Cell Lines

“…Our central hypothesis is that factors secreted from normal FBs that express CD36 could be utilized as an alternative strategy to reprogram the microenvironment and suppress the growth of certain breast tumors. CD36 is a scavenger receptor that mediates lipid uptake, is expressed in multiple cancer types [ 7 ], and accelerates tumor growth [ 8 ]. However, this receptor is downregulated in tumor-associated FBs and has been suggested as a CAF marker [ 9 ].…”

Prognostic Impact of CD36 Immunohistochemical Expression in Patients with Muscle-Invasive Bladder Cancer Treated with Cystectomy and Adjuvant Chemotherapy

“…Recently, the prognostic value and immunological role of CD36 has been evaluated in multiple tumors and paratumoral tissue. The results indicate that, in fact, the influence of CD36 on patient prognosis depends on the type of cancer [37].…”