Banca de QUALIFICAÇÃO: RAUL MAIA FALCÃO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : RAUL MAIA FALCÃO
DATE: 26/08/2022
TIME: 10:00
LOCAL: http://meet.google.com/kit-ckyq-oqb10
TITLE:

Molecular characterization applied to the identification of expression profiles in uterine leiomyosarcoma using transcriptomics and proteomics

KEY WORDS:

Uterine leiomyosarcoma, immunoproteasome, extracellular matrix, precision oncology, biomarkers, therapeutic targets

PAGES: 42
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Uterine sarcoma is a malignant tumor with an aggressive clinical course, representing around 3-7% of all malignant uterine neoplasms. Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcoma of mesenchymal origin. The diagnosis of uLMS occurs by chance when performing hysterectomy for leiomyomas – benign tumors – and confirmed by histopathological features such as cell atypia, mitotic index and tumor cell necrosis. From a molecular point of view, developing effective studies to search for diagnostic biomarkers of uLMS is a challenge due to the molecular heterogeneity of the tumor and scarcity of samples. The study of uLMS will help to find unique molecular signatures in malignant cells and relate this information to clinical features. Our objective is to characterize gene and protein expression profiles as well to investigate potential genes related to malignancy in uLMS samples. Our preliminary results point to a profile of differentially expressed protein between 3 subtypes of tumor. Besides that, the PSMB9 gene (MIM:177045), also known as LMP2, was found to be overexpressed and with heterogeneous values of gene expression in the uLMS group. Quartile groups showed no significant difference between high and low PSMB9 expression values at 3-year and 5-year survival times. However, the presence of CD8+ tumor-infiltrating lymphocytes (TILs) contributed to the recognition of tumor cells and the immune system response. This presence was observed due to significant differences associated with better survival when considering the CD8+/PSMB9 ratio at the 3-year survival time. Furthermore, the prediction of decreased expression of PSMB9 at the protein level showed, together with a proto-oncogene tyrosine-protein kinase (SRC), an inhibition of the extracellular matrix (ECM) pathway. These findings contribute to the understanding of the immune response as well as ECM cellular interactions in uLMS. Taken together, our analysis showed that CD8+ T cell infiltration and PSMB9 levels suggest further analysis in relation to translational studies for immune therapies.

COMMITTEE MEMBERS:
Presidente - 3063244 - TETSU SAKAMOTO
Interno - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN