CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma

Yoshida, Tatsushi; Yokobori, Takehiko; Saya, Hideyuki; Kuriyama, Kinya; Kumakura, Yuji; Honjo, Hiroaki; Hara, Keigo; Sakai, Makoto; Miyazaki, Tatsuya; Obinata, Hideru; Erkhem-Ochir, Bilguun; Gombodorj, Navchaa; Sohda, Makoto; Saeki, Hiroshi; Kuwano, Hiroyuki; Shirabe, Ken

doi:10.1245/s10434-020-08711-3

Cited by 22 publications

(28 citation statements)

References 24 publications

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“…Taking this into consideration, it fits the correlation with the grading, the T-status, and the general aggressiveness. Similar findings have been shown for oesophageal squamous cell carcinoma [31].…”

Section: Discussionsupporting

confidence: 89%

“…Even though CD36 expression correlated significantly in the log-rank analysis with a poorer progression-free survival, the multivariate analysis indicated that it is not an independent prognostic factor. This is most likely due to the high correlation with a positive N-status [31]. Within the N+ group, the progression-free survival differed between high and low CD36 expression, but there are only few cases with low CD36 expression and lymph node metastasis.…”

Section: Discussionmentioning

confidence: 96%

“…This is an average amount compared with other entities. Published studies present a range of CD36 expression, from 19% in squamous cell carcinoma of the esophagus to 70% in cervical carcinoma [27,31].…”

Section: Discussionmentioning

confidence: 99%

“…These findings might indicate a role of pre-and post-therapeutic nutrition and the influence on disease progression. This could be relevant for patients with cancer in the digestive tract or head/neck region where, due to cachexia, high doses of FA for weight gain are admitted [31].…”

Section: Discussionmentioning

confidence: 99%

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Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Haidari

Tröltzsch

Knösel

et al. 2021

Cancers

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Purpose: To investigate the expression pattern of CD36 in a patient population with oral squamous cell carcinoma (OSCC) and to correlate CD36 expression with clinical and histopathological parameters. The hypothesis was that CD36 expression correlates with the occurrence of lymph node metastasis. Methods: To address the study objectives, a retrospective cohort study was conducted. Study variables included demographic, histopathological and survival data. CD36 expression patterns were assessed by immunohistochemistry on tissue microarrays (TMA). Logistic regression analysis, survival analysis and Cox proportional hazards model were performed. Results: High CD36 expression correlated significantly with a higher T-status, grading and occurrence of lymph node metastasis. The logistic regression with binary N status as a dependent variable showed that high CD36 expression increased the chance for lymph node metastasis 45-fold (OR = 44.7, 95% CI: 10.0–316). Patients with high CD36 expression had lower probabilities of progression-free survival. CD36 had a small and non-significant independent influence on progression-free survival. Conclusions: CD36 is expressed in OSCC and correlates with tumor grading, T-status, and especially the occurrence of lymph node metastasis. CD36 may be useful for risk stratification regarding lymph node metastasis in OSCC.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Haidari

Tröltzsch

Knösel

et al. 2021

Cancers

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“…Its biological functions involve lipid uptake, immune recognition, inflammation, molecular adhesion and apoptosis, inflammatory response, apoptosis phagocytosis, angiogenesis, energy metabolism, and tumor metastasis [2][3][4]. CD36 not only promotes tumor metastasis and treatment resistance by promoting lipid uptake and FA oxidation, but also inhibits angiogenesis by binding with TSP-1, thus inducing tumor microvascular endothelial cell apoptosis or blocking the vascular endothelial growth factor receptor 2 pathway [5][6][7]. In addition, CD36-driven lipid metabolism reprogramming and the function of tumor-associated immune cells lead to tumor immune tolerance and tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

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

Chen¹,

Liao²,

Huang³

et al. 2021

J. Cancer

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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.

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Lipid metabolism–related lncRNA SLC25A21‐AS1 promotes the progression of oesophageal squamous cell carcinoma by regulating the NPM1/c‐Myc axis and SLC25A21 expression

Liu

Fang

et al. 2022

Clinical & Translational Med

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Background Obesity alters metabolic microenvironment and is thus associated with several tumours. The aim of the present study was to investigate the role, molecular mechanism of action, and potential clinical value of lipid metabolism–related long non‐coding RNA (lncRNA) SLC25A21‐AS1 in oesophageal squamous cell carcinoma (ESCC). Methods A high‐fat diets (HFDs)‐induced obesity nude mouse model was established, and targeted metabolomics analysis was used to identify critical medium‐long chain fatty acids influencing the growth of ESCC cells. Transcriptomic analysis of public dataset GSE53625 confirmed that lncRNA SLC25A21‐AS1 was a lipid metabolism–related lncRNA. The biological function of lncRNA SLC25A21‐AS1 in ESCC was investigated both in vivo and in vitro. Chromatin immunoprecipitation(ChIP)assay, RNA‐pull down, mass spectrometry, co‐IP, and RNA IP(RIP) were performed to explore the molecular mechanism. Finally, an ESCC cDNA microarray was used to determine the clinical prognostic value of SLC25A21‐AS1 by RT‐qPCR. Results Palmitic acid (PA) is an important fatty acid component of HFD and had an inhibitory effect on ESCC cell lines. LncRNA SLC25A21‐AS1 expression was downregulated by PA and associated with the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, SLC25A21‐AS1 interacted with nucleophosmin‐1 (NPM1) protein to promote the downstream gene transcription of the c‐Myc in the nucleus. In the cytoplasm, SLC25A21‐AS1 maintained the stability of SLC25A21 mRNA and reduced the intracellular NAD+/NADH ratio by influencing tryptophan catabolism. Finally, we demonstrated that high expression of SLC25A21‐AS1 promoted resistance to cisplatin‐induced apoptosis and was correlated with poor tumour grade and overall survival. Conclusions HFD/PA has an inhibitory effect on ESCC cells and SLC25A21‐AS1 expression. SLC25A21‐AS1 promotes the proliferation and migration of ESCC cells by regulating the NPM1/c‐Myc axis and SLC25A21 expression. In addition, lncRNA SLC25A21‐AS1 may serve as a favourable prognostic biomarker and a potential therapeutic target for ESCC.

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CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma

Cited by 22 publications

References 24 publications

Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma

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

Lipid metabolism–related lncRNA SLC25A21‐AS1 promotes the progression of oesophageal squamous cell carcinoma by regulating the NPM1/c‐Myc axis and SLC25A21 expression

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