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| Página principal > Artículos > Artículos publicados > Succinate Pathway in Head and Neck Squamous Cell Carcinoma : |
(Universitat Rovira i Virgili) (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (Universitat Rovira i Virgili) (Universitat Rovira i Virgili) (Hospital de Tortosa Verge de la Cinta) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigació Biomèdica Sant Pau) (Hospital de Tortosa Verge de la Cinta) (Universitat Rovira i Virgili) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (Hospital Clínic i Provincial de Barcelona)| Fecha: | 2021 |
| Resumen: | Emerging evidence points to succinate as an important oncometabolite in cancer development; however, the contribution of the succinate-SUCNR1 axis to cancer progression remains unclear. Head and neck squamous cell carcinoma (HNSCC) is associated with disease and treatment-related morbidity so there is an urgent need for innovation in treatment and diagnosis practices. Our aim was to evaluate the potential of the succinate-related pathway as a diagnostic and prognostic biomarker in HNSCC. The circulating succinate levels are increased in HNSCC, being a potential noninvasive biomarker for HNSCC diagnosis. Moreover, the succinate receptor (SUCNR1) and genes related to succinate metabolism, which are predominantly expressed in the tumoral mucosa as compared with healthy tissue, are positively associated with plasma succinate. Remarkably, we found that SUCNR1 and SDHA expression levels predict prognosis. Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77. 1% [95% CI: 48. 9-100. 0] vs. 16. 7% [95% CI: 0. 0-44. 4], p = 0. 018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis. |
| Ayudas: | Instituto de Salud Carlos III PI15/02047 Instituto de Salud Carlos III PI18/0844 Instituto de Salud Carlos III PI19/01661 Instituto de Salud Carlos III CB07708/0012 Instituto de Salud Carlos III CP10/00438 Instituto de Salud Carlos III CPII16/00008 Ministerio de Economía, Industria y Competitividad RTI2018-093919 |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | Oncometabolite ; Succinate ; Succinate receptor ; Metabolism ; Head and neck cancer ; Treatment ; Prognosis |
| Publicado en: | Cancers, Vol. 13 (april 2021) , ISSN 2072-6694 |
