Banca de QUALIFICAÇÃO: MATHEUS GIBEKE SIQUEIRA DALMOLIN
Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.STUDENT : MATHEUS GIBEKE SIQUEIRA DALMOLIN
DATE: 31/01/2022
TIME: 11:00
LOCAL: meet.google.com/iou-qxkp-owe
TITLE:
Systems biology-based analysis highlights altered processes that impact overall survival of Ewing Sarcoma patients
KEY WORDS:
Ewing's sarcoma, autophagy, double break repair, immune response, hippo pathway
PAGES: 20
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:
Ewing's Sarcoma (ES) is a highly aggressive tumor that affects bones and soft tissues, being the second most frequent pediatric bone neoplasm. It is characterized by the presence of a translocation involving the EWS gene and another gene from the ETS family, usually FLI1. Although treatment for localized disease has proven to be effective, the long- term survival of patients with metastatic SE or who have relapsed is still very low. Thus, it is necessary to investigate the main differences at the systemic level between patients with different outcomes, to indicate new paths that can lead to more effective and individualized treatment protocols according to the level of tumor aggressiveness. In order to investigate the differences between long survival and short survival from a systemic perspective, we applied transcriptogramer methodology to microarray data from three independent cohorts of SE biopsies containing outcome and overall survival (OS) metadata: GSE63155, GSE63156 and GSE17618 . The cohorts were classified into two groups according to Overall Survival (OS): long survival (SL) - SG > 5 years and short survival (SC) - SG <5 years. The comparison between the two outcomes was performed using The Transcriptogramer V.1 software, other analyzes were performed in the R environment. There was a significant difference in the gene expression profile between the groups (SL and SC) in the three cohorts. We selected clusters of differentially expressed genes (CGDE) common in transcriptograms and enriched each of them for the GO terms. We observed the upregulation of several pathways related to checkpoint, DNA damage response, double-strand break repair and recombinational repair. We also found downregulated processes that were related to GPI anchor, apoptosis, ubiquitination, antigen processing and presentation, regulation of innate immune response and autophagy. We interrogated the genes of each of the clusters against the regulatory network of SE master regulators (Dantas et al., 2021) and enriched the filtered genes. The Hippo pathway stood out among the positively regulated pathways. For the downregulated pathways, the autophagy pathway was also found through the enrichment of genes regulated by at least one master regulator. Autophagy in general was the process that stood out the most in enrichments and its negative regulation in patients with short survival opens new horizons to explore the already controversial role of autophagy in SE.
BANKING MEMBERS:
Presidente - 609.016.910-20 - MARIALVA SINIGAGLIA - UFRGS
Interno - 059.501.268-07 - JOSÉ MIGUEL ORTEGA - UFMG