Role of Growth and Differentiation Factor 15 (GDF-15) and MicroRNAs in the pathogenesis of sarcopenia in lung cancer patients.

Anno
2017
Proponente Maurizio Muscaritoli - Professore Ordinario
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Alessio Molfino Componenti il gruppo di ricerca / Participants in the research project
Massimo Vergine Componenti il gruppo di ricerca / Participants in the research project
Maria Ida Amabile Dottorando/Assegnista/Specializzando componente il gruppo di ricerca / PhD/Assegnista/Specializzando member of the research group
Edoardo Rosato Componenti il gruppo di ricerca / Participants in the research project
Componente Qualifica Struttura Categoria
Cesarina Ramaccini Tecnico di laboratorio Dipartimento di Medicina Clinica Altro personale Sapienza o esterni / Other personnel Sapienza or other institution
Abstract

Cancer cachexia is a severe and disabling clinical condition that frequently accompanies the development of cancer. The hallmark of cancer cachexia is the loss of muscle mass and function with or without concomitant fat mass loss. Sarcopenia identifies a clinical condition of progressive and generalized loss of muscle mass associated with reduced muscle strength and/or physical performance. The systemic effects of cancer cachexia are the result of circulating factors, such as pro-inflammatory cytokines, responsible for modifying central mechanisms that regulate appetite and energy expenditure and promoting the activation of several transcription factors and mediators directly involved in muscle mass loss such as Growth and Differentiation Factor 15 (GDF-15). GDF-15 is associated with weight loss, decreased muscle mass and strength, and poor survival in cancer patients, serving as a prognostic indicator in cancer patients and as a potential therapeutic target for cancer-related weight loss. Moreover, GDF-15 is able to suppress the transcription of various muscle tissue microRNAs (miRs) resulting in loss of muscle mass and promoting muscle atrophy, especially in lung cancer. Identification and dosage of serum concentrations of circulating miRs and GDF-15 could be useful as potential biomarkers in the diagnosis and prognosis of lung cancer patients and as potential therapeutic targets. Naïve lung cancer patients will be enrolled and divided in sarcopenic and non sarcopenic. Evaluation of skeletal muscle mass will be calculated. Dosage of proinflammatory cytokines and GDF-15 levels will be performed, and muscle specific miRs on serum, saliva and urine samples will be investigated. Overall survival and progression-free survival data will be collected. These results will be useful for subsequent studies aimed at reducing morbidity, mortality and improving the quality of life of cancer patients through specific and personalized nutritional and pharmacological interventions

ERC
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