Sphingolipids signature in plasma and tissue as diagnostic and prognostic tools in oral squamous cell carcinoma

Autor(es)

Faedo, Raquel Roman ^[1] ; da Silva, Gabriel ^[1] ; da Silva, Rodrigo Moreira ^[2] ; Ushida, Tatiane Resende ^[1] ; da Silva, Ricardo Roberto ^[2] ; Lacchini, Riccardo ^[3] ; Matos, Leandro Luongo ^[4] ; Kowalski, Luiz Paulo ^[4] ; Lopes, Noberto Peporine ^[2] ; Leopoldino, Andreia Machado ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Av Cafe S-N, Bloco A, Sala 99A, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Nucleo Pesquisa Prod Nat & Sintet NPPNS, Dept Ciencias Biomol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Dept Psychiat Nursing & Human Sci, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Med LIM28, Hosp Clin HCFMUSP, Head & Neck Surg Dept, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[5] Reg Blood Ctr Ribeirao Preto, Ctr Cell Based Therapy, CEPID FAPESP, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS; v. 1867, n. 1 JAN 2022.
• Citações Web of Science: 0

Resumo

Enzymes related to sphingolipids metabolism has been suggested as altered in oral squamous cell carcinoma (OSCC). However, clinical relevance of diverse sphingolipids in OSCC is not fully known. Here, we evaluated sphingolipidomics in plasma and tumor tissues as a tool for diagnosis/prognosis in OSCC patients. Plasma was obtained from 58 controls and 56 OSCC patients, and paired tumor and surgical margin tissues (n = 42). The levels of 28 sphingolipids molecules were obtained by mass spectrometry. Furthermore, sphingolipids were analyzed with clinical and pathological characteristics to search the potential for diagnosis and prognosis. Lower levels of 17 sphingolipids was found in the plasma of OSCC patients compared to controls while four were elevated in tumor tissues. C18:0 dyhidroceramide and C24:0 lactosylceramide in plasma were associated with perineural invasion, while tissue levels of ceramide and dyhidroceramide were associated with advanced tumor stage and perineural invasion. High plasma levels of C24:0 ceramide (HR = 0.10, p = 0.0036) and C24:1 glucosylceramide (HR = 6.62, p = 0.0023), and tissue levels of C24:0 dyhidroceramide (HR = 3.95, p = 0.032) were identified as independent prognostic factors. Moreover, we identified signatures composed by i) sphinganine-1-phosphate and C16 ceramide-1-phosphate in plasma with significant diagnostic accuracy, while ii) C24:0 ceramide, C24:0 dyhidroceramide, and C24:1 glucosylceramide plasma levels, and iii) C24:0 dyhidrosphingomyelin and C24:0 ceramide tissue levels showed value to predict survival in patients aged 60 years or older. We proposed the sphingolipids signatures in plasma and tumor tissues as biomarkers candidates to diagnosis and prognosis in OSCC. (AU)

• Processo FAPESP: 17/18922-2 - Desenvolvimento de uma plataforma computacional modular extensível para análises de experimentos de metabolômica e metagenômica: inovando com a descoberta de novas atividades enzimáticas e produtos naturais de interesse farmacêutico derivados
• Beneficiário: Ricardo Roberto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Jovens Pesquisadores
• Processo FAPESP: 18/17480-9 - Estudo da SET e esfingolipídeos em câncer de cabeça e pescoço: sinalização, alvos e terapia antitumoral
• Beneficiário: Gabriel da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/19103-2 - SET e esfingolipídeos em câncer de cabeça e pescoço: sinalização, alvos e terapia antitumoral
• Beneficiário: Andréia Machado Leopoldino
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/05026-4 - Desenvolvimento de uma plataforma computacional modular extensível para análises de experimentos de metabolômica e metagenômica: Inovando com a descoberta de novas atividades enzimáticas e produtos naturais de interesse farmacêutico derivados
• Beneficiário: Ricardo Roberto da Silva
• Modalidade de apoio: Bolsas no Brasil - Programa BIOTA - Jovens Pesquisadores
• Processo FAPESP: 18/03278-3 - Perfil de esfingolipídios no câncer de cabeça e pescoço
• Beneficiário: Raquel Roman Faedo
• Modalidade de apoio: Bolsas no Brasil - Mestrado