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| Author(s): |
Sarah Santiloni Cury
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Botucatu. 2019-03-15. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu |
| Defense date: | 2019-02-26 |
| Advisor: | Robson Francisco Carvalho |
| Abstract | |
Cachexia is a metabolic syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of adipose tissue) that cannot be fully reversed by conventional nutritional support, most found in patients with advanced cancer. The molecular pathways of cancer cachexia are not completely known. The advances in genomic, transcriptomic and proteomic studies in cancer have helped in understanding the relationship of the tumor's secretome with changes in organs and tissues adjacent to or distant from the tumor. Evidences show that components of the tumor secretome, including pro-inflammatory cytokines, play a key role in metabolic alterations that result in sarcopenia (loss of muscle mass and function) of cachectic patients. 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) 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, 89 CTs from patients with NSCLC, available on the TCIA (The Cancer Imaging Archive) platform were used to measure the pectoralis muscle area, and to select patients with low or high muscularity. Differential gene expression analysis of tumor from these same patients was performed to select transcripts with increased expression in the tumor of low muscularity patients. Transcripts related to the tumor's secretome were selected through in silico prediction analyzes. In addition, these molecules were evaluated for their functional classification and relationship to the clinical data of each patient. Our results demonstrated the relevance of Interleukin-8 as potential biomarkers of cachexia associated with poor prognosis of patients with NSCLC. These data are useful for early detection of cachexia, which may have clinical impact in the management of patients with NSCLC. (AU) | |
| FAPESP's process: | 17/21223-9 - Identification of potential secretome biomarkers in non-small-cell lung cancer cachexia |
| Grantee: | Sarah Santiloni Cury |
| Support Opportunities: | Scholarships in Brazil - Master |