Sphingolipids signature in plasma and tissue as diagnostic and prognostic tools in oral squamous cell carcinoma |
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| Institution: | 1. Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Brazil;2. Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil;3. Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil;4. Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas HCFMUSP, Faculdade de Medicina (LIM28), Universidade de São Paulo, São Paulo, Brazil;5. CEPID-FAPESP, Center for Cell Based Therapy, Regional Blood Center of Ribeirão Preto, SP, Brazil;1. Department of Neurology and Neuroscience, Fujita Health University Hospital, Aichi, Japan;2. Faculty of Pharmacy, Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science and Frontier Research Center for Advanced Material and Life Science, Hokkaido University, Hokkaido, Japan;1. Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA 02118, USA;2. Endocrinology Department of the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;3. CIBER of Diabetes and Metabolic Diseases (CIBERDEM), Spain;4. Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau, CIBERDEM, Barcelona, Spain;1. Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA;2. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China;3. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA;4. Biochemistry and Cell Biology Program, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA;1. Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium;2. Quebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, Canada;3. Centre NUTRISS, Institute of Nutrition and Functional Foods, Université Laval, Quebec City, QC G1V 0A6, Canada;4. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy;1. Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy;2. INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d''Oro 305, 00136 Rome, Italy;3. Metabolism Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden;4. Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy;5. National Cancer Research Center, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy |
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| Abstract: | 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. |
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