Succinate Pathway in Head and Neck Squamous Cell Carcinoma: Potential as a Diagnostic and Prognostic Marker

Cancers

FrancescXavier Avilés-Jurado¹  Sonia Fernández-Veledo²  Ester Benaiges²  Joan Vendrell²  Victoria Ceperuelo-Mallafré²  Marina Cámara³  Ximena Terra⁴  Neus Basté⁵  Josep Gumà⁶  Isabel Vilaseca⁷  JoanCarles Flores⁸  Carla Merma⁸  Xavier León⁹  Paola Castillo^1,10  Marylène Lejeune^1,11  Ramon Bosch^1,11  Izaskun Valduvieco^1,12 

[1] Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM), 28029 Madrid, Spain;Department of Endocrinology and Nutrition, Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain;Maxillofacial Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain;MoBioFood Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, Campus Sescel·lades, 43007 Tarragona, Spain;Oncology Department, IDIBAPS, Hospital Clínic de Barcelona, 08036 Barcelona, Spain;Oncology Department, Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Sant Joan de Reus, 43204 Reus, Spain;Otorhinolaryngology Department, UB, IDIBAPS, Hospital Clínic de Barcelona, 08036 Barcelona, Spain;Otorhinolaryngology Head-Neck Surgery Department, Hospital Universitari de Tarragona Joan XXIII, Insitut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43005 Tarragona, Spain;Otorhinolaryngology Head-Neck Surgery Department, Hospital de la Santa Creu i Sant Pau and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, MICINN, ISCIII), Universitat Autònoma de Barcelona, 08041 Barcelona, Spain;Pathology Department, Hospital Clínic de Barcelona, IDIBAPS, 08036 Barcelona, Spain;Pathology Department, Plataforma de Estudios Histológicos, Citológicos y de Digitalización, Hospital de Tortosa Verge de la Cinta, Institut d’Investigació Sanitària Pere Virgili (IISPV), URV, 43500 Tortosa, Spain;Radiation Oncology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain;

关键词: oncometabolite;    succinate;    succinate receptor;    metabolism;    head and neck cancer;    treatment;   

DOI  :  10.3390/cancers13071653

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown