Identification of potential secretome biomarkers in non-small-cell lung cancer cachexia

Abstract

Cachexia is a metabolic syndrome characterized by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support, most found in patients with advanced cancer. The cancer cachexia molecular pathways are not completely known, however, advances in genomic, transcriptomic and proteomic studies in cancer have helped in understanding the relationship of the tumor's secretome and distant organs. Evidences show that components of the tumor secretome, including proinflammatory cytokines, play a key role in metabolic alterations that result in loss of muscle mass and function of cachectic patients. Among the types of tumors with a high incidence of muscle atrophy due to cachexia, stands out the lung cancer, which is the most commonly found in the population. Loss of skeletal muscle mass is important prognostic factor for cachexia in patients with non-small cell lung cancer (NSCLC), thus the evaluation of muscular area using computed tomography (CT) scans has been effective in determine survival and the presence of cachexia and sarcopenia in these patients. Therefore, our hypothesis is that the integration of clinical and prognostic data, pectoralis muscle area obtained by CTs, and tumor transcriptional profile will allow the identification of potential biomarkers of cachexia in the secretome of non-small cell lung carcinomas. To do this, 195 CTs from patients with NSCLC, available on the TCIA (The Cancer Imaging Archive) platform will be used to measure the pectoralis muscle area, and to select patients with low or high muscularity. Differential expression analysis of tumor genes from these same patients will be performed to select transcripts with increased expression in the tumor of low muscularity patients; from this analysis will be selected transcripts related to the tumor's secretome through in silico analyzes that predicts secreted proteins. In addition, these molecules will be evaluated for their functional classification and relationship to the clinical data of each patient. These results may be important for the development of future therapeutic strategies aiming to minimize the loss of muscle mass, increase survival, and improve the quality of life of cancer cachexia patients. (AU)