Banca de DEFESA: RAUL MAIA FALCÃO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : RAUL MAIA FALCÃO
DATE: 14/03/2025
TIME: 13:30
LOCAL: https://meet.google.com/fma-yzuk-dhm
TITLE:

Identifying Biomarkers and Molecular Signatures in Uterine Leiomyosarcoma by Multi-omics Approach

KEY WORDS:

Uterine leiomyosarcoma; immunoproteasome; extracellular matrix; precision oncology; biomarkers; therapeutic targets.

PAGES: 107
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Uterine sarcoma is a malignant tumor with aggressive clinical progression, accounting for approximately 3–7% of all malignant uterine neoplasms. Uterine leiomyosarcoma (uLMS) is the most common mesenchymal subtype of uterine sarcoma. The diagnosis of uLMS is often incidental, occurring during hysterectomy for leiomyomas (LM) - benign tumors - and confirmed through histopathological features such as cellular atypia, mitotic index, and tumor cell necrosis. From a molecular perspective, developing effective studies to identify diagnostic biomarkers for uLMS is challenging due to the tumor's molecular heterogeneity and limited sample availability. In this study, we conducted a comprehensive multi-omics integration analysis (genomics, transcriptomics, and proteomics) using fresh tumors to uncover the molecular characteristics of uLMS. The results identified two actionable therapeutic targets, IDH1_p.Arg132Cys and KRAS_p.Gly12Cys, in metastatic patients. Homologous recombination deficiency (HRD) was observed as the most predominant genomic signature. Additionally, 80% of the samples exhibited a chromothripsis signature, reinforcing the aneuploid phenotype of these tumors. uLMS tumors were characterized by a high proliferation score and elevated expression of the Ki67 gene (MIM:176741), which were associated with worse prognosis. Furthermore,
a high frequency of in-frame fusion events involving the EEF1A1 gene (MIM:130590) was reported. The multi-omics integration analysis identified amplification of the CTHRC1 gene (MIM:610635), which had a negative impact on disease prognosis. Lastly, the PSMB9 gene (MIM:177045) was found to be overexpressed with heterogeneous gene expression values in the uLMS group. Quartile groups showed no significant differences between high and low PSMB9 expression values in terms of 3- and 5-year survival times. However, the presence of tumor-infiltrating lymphocytes (TILs) CD8+ contributed to tumor cell recognition and immune system response. This presence was associated with significant differences linked to better survival outcomes when considering the CD8+/PSMB9 ratio in 3-year survival. These findings contribute to a better  understanding of immune response mechanisms and extracellular matrix (ECM) interactions, suggesting that uLMS patients could benefit from individualized precision medicine.

 

 

COMMITTEE MEMBERS:
Externo à Instituição - SÉRGIO DE SÁ LEITÃO PAIVA JÚNIOR - UFRPE
Interna - 1365498 - BEATRIZ STRANSKY FERREIRA
Presidente - 2170415 - Jorge Estefano de Santana Souza
Externo à Instituição - MARIANA LIMA BORONI MARTINS - INCA
Externo à Instituição - VALDIR BALBINO