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

Haidari, Selgai; Tröltzsch, Matthias; Knösel, Thomas; Liokatis, Paris; Kasintsova, Anastasia; Eberl, Marian; Ortner, Florian; Otto, Sven; Fegg, Florian; Boskov, Marko; Probst, Florian

doi:10.3390/cancers13164125

Cited by 16 publications

(8 citation statements)

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“…Other risk factors for occult metastases are histopathological parameters such as lymphovascular invasion [ 15 ] and histopathological grading [ 16 ]. Furthermore, several gene and marker expression patterns have already been studied as risk factors for occult metastases [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Haidari

Obermeier

Kraus

et al. 2022

Cancers

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The impact of neck involvement and occult metastasis (OM) in patients with oral squamous cell carcinoma (OSCC) favors an elective neck dissection. However, there are barely any existing data on survival for patients with OM compared with patients with positive lymph nodes detected preoperatively. This study aims to compare survival curves of patients suffering from lymph nodal metastases in a preoperatively N+ neck with those suffering from OM. In addition, clinical characteristics of the primary tumor were analyzed to predict occult nodal disease. This retrospective cohort study includes patients with an OSCC treated surgically with R0 resection with or without adjuvant chemoradiotherapy between 2010 and 2016. Minimum follow-up was 60 months. Kaplan–Meier analysis was used to compare the survival between patients with and without occult metastases and patients with N+ neck to those with occult metastases. Logistic regression was used to detect potential risk factors for occult metastases. The patient cohort consisted of 226 patients. Occult metastases occurred in 16 of 226 patients. In 53 of 226 patients, neck lymph nodes were described as suspect on CT imaging but had a pN0 neck. Higher tumor grading increased the chance of occurrence of occult metastasis 2.7-fold (OR = 2.68, 95% CI: 1.07–6.7). After 12, 24, 48 and 60 months, 82.3%, 73.8%, 69% and 67% of the N0 patients, respectively, were progression free. In the group with OM occurrence, for the same periods 66.6%, 50%, 33.3% and 33.3% of the patients, respectively, were free of disease. For the same periods, respectively, 81%, 63%, 47% and 43% of the patients in the N+ group but without OM remained disease free. The predictors for progression-free survival were a positive N status (HR = 1.44, 95% CI: 1.08–1.93) and the occurrence of OM (HR = 2.33, 95% CI: 1.17–4.64). The presence of occult metastasis could lead to decreased survival and could be a burdening factor requiring treatment escalation and a more aggressive follow-up than nodal disease detected in the preoperative diagnostic imaging.

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Section: Introductionmentioning

confidence: 99%

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Haidari

Obermeier

Kraus

et al. 2022

Cancers

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“…In a retrospective cohort study with primary diagnosed OSCC, patients with high CD36 expression displayed lower probability of progression-free survival, with only 34% of them alive or recurrence-free at 60 months. The study also demonstrated a 45-fold increased risk of lymph node metastasis in the CD36-high group ( Haidari et al, 2021 ).…”

Section: Cd36 In Specific Cancer Typesmentioning

confidence: 67%

“…In several types of cancer, there is a positive correlation between tumor CD36 expression and poor clinical outcome ( Abd El-Aziz et al, 2013 ; Hale et al, 2014 ; Deng et al, 2019 ; Luanpitpong et al, 2019 ; Haidari et al, 2021 ; Jeong et al, 2021 ; Luo et al, 2021 ; Yang et al, 2021 ; Pardo et al, 2022 ). Mechanistically, CD36 participates in tumor development by favoring the lipid intake in cancer cells and promoting a switch in lipid metabolism to settle the increasing energetic demand of the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…CD36 has been related to cell proliferation and tumor growth kinetics in several types of cancers ( Deng et al, 2019 ; Watt et al, 2019 ; Drury et al, 2020 ; Ghoneum et al, 2020 ; Sakurai et al, 2020 ; Gyamfi et al, 2021 ; Haidari et al, 2021 ; Luo et al, 2021 ; Drury et al, 2022 ). There is also evidence of a positive correlation between CD36 expression/activation and EMT induction in cancer cells, where CD36-mediated FA uptake/accumulation and the consequent energetic reprogramming are key for the acquisition of a more aggressive phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Role of CD36 in cancer progression, stemness, and targeting

Guerrero-Rodriguez

Mata-Cruz

Pérez‐Tapia

et al. 2022

Front. Cell Dev. Biol.

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CD36 is highly expressed in diverse tumor types and its expression correlates with advanced stages, poor prognosis, and reduced survival. In cancer cells, CD36: 1) increases fatty acid uptake, reprogramming lipid metabolism; 2) favors cancer cell proliferation, and 3) promotes epithelial-mesenchymal transition. Furthermore, CD36 expression correlates with the expression of cancer stem cell markers and CD36+ cancer cells display increased stemness functional properties, including clonogenicity, chemo- and radioresistance, and metastasis-initiating capability, suggesting CD36 is a marker of the cancer stem cell population. Thus, CD36 has been pointed as a potential therapeutic target in cancer. At present, at least three different types of molecules have been developed for reducing CD36-mediated functions: blocking monoclonal antibodies, small-molecule inhibitors, and compounds that knock-down CD36 expression. Herein, we review the role of CD36 in cancer progression, its participation in stemness control, as well as the efficacy of reported CD36 inhibitors in cancer cell cultures and animal models. Overall, the evidence compiled points that CD36 is a valid target for the development of new anti-cancer therapies.

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“…This study included 83 patients (female n = 33, male n = 50; with a mean age of 61 ± 15 years) diagnosed with primary oral squamous cell carcinoma (OSCC). This cohort has already been investigated in another study regarding the expression of CD36 20 . The tumor was mostly localized in the alveolar process of the mandible ( n = 29/83, 34.9%), followed by the floor of the mouth ( n = 19/83; 22,9%) and then the anterior 2/3 of the tongue ( n = 15/83; 18.1%), the hard palate and soft palate ( n = 8/83; 9.6%), and finally, the alveolar process of the maxilla ( n = 12/83; 14.5%).…”

Section: Resultsmentioning

confidence: 99%

Cancer testis antigen (PRAME) as an independent marker for survival in oral squamous cell carcinoma (OSCC)

Haidari

Tröltzsch

Fliefel

et al. 2022

J Oral Pathology Medicine

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Background The objective was to assess the expression patterns of the cancer testis antigen PRAME, NY‐ESO1, and SSX2 in oral squamous cell carcinoma (OSSC) and to correlate the expression with clinical and histopathological parameters including progression‐free survival analysis. Methods The study variables of this retrospective cohort study (n = 83) included demographic data, histopathological data, and information on progression‐free survival. PRAME expression patterns were rated based on immunohistochemistry on tissue microarrays (TMA). The survival rate was assessed by Kaplan–Meier method and Cox regression model. The primary predictor variable was defined as the expression of PRAME and the outcome variable was progression‐free survival. Results Analysis of progression‐free survival using Kaplan–Meier method showed that patients with positive expression of PRAME had lower probabilities of progression‐free survival (p < 0.001). According to the Cox regression model, the level of PRAME expression had a considerable and significant independent influence on progression‐free survival (positive PRAME expression increasing the hazards for a negative outcome by 285% in our sample; HR = 3.85, 95% CI: 1.45–10.2, p = 0.007). The expression of SSX2 (n = 1) and NY‐ESO‐1 (n = 5) in our samples was rare. Conclusion PRAME is expressed in OSCC and appears to be a suitable marker of progression‐free survival, correlates with severe course, and may allow identification of high‐risk patients with aggressive progression.

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

Cited by 16 publications

References 36 publications

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Role of CD36 in cancer progression, stemness, and targeting

Cancer testis antigen (PRAME) as an independent marker for survival in oral squamous cell carcinoma (OSCC)

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