NUMERO: #20250441

Título: BASAL CELL ADENOMA: UNVEILING TUMORIGENIC PATHWAYS AND POTENTIAL THERAPEUTIC TARGETS THROUGH PROTEOGENOMICS

Nome do Apresentador: Gustavo de Souza VIEIRA

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Patologia Oral

Resumo: Objective: Perform whole-exome sequencing (WES) and mass spectrometry (LC-MS/MS) on basal cell adenoma (BCA) to identify potential molecular alterations and signaling pathways, enhancing the understanding of its pathogenesis and highlighting potential therapeutic opportunities.
Study Design: One fresh BCA tumor was analyzed by WES and six FFPE BCA samples by LC-MS/MS. Genomic variants were identified using ENSEMBL, and proteomic analysis was conducted with MaxQuant/Perseus. Associations and enrichment analysis employed Gene Ontology/KEGG knowledgebases (p<0.05).
Results: WES identified 1,277,797 gene variants, with 24.7% being novel. Most variants were synonymous (53%) or missense (45%). Filtering actionable genes through the MSK-IMPACT® profile, 139 mutated cancer-related genes were found, including the common CTNNB1 gene. Enrichment was observed in the VEGF (p=3.89e-11), p53 (p=1.70e-12), Wnt (p=2.84e-06), and PI3-Kinase (p=2.17e-05) pathways. LC-MS/MS identified 2615 proteins, 28 unique. There were 338 upregulated proteins compared to normal salivary glands, showing enrichment in the PI3K-Akt pathway (p=0.0071). By analyzing upregulated/exclusive proteins (338) against mutated coding genes with moderate/high impact (8229), 104 matches were found. The PI3K-Akt pathway was highlighted through proteogenomic analysis (p=0.0127).
Conclusion: Proteogenomics identified potential signaling pathways, including novel PI3K-Akt, for BCA pathogenesis and targeted therapies. Further studies are recommended to validate these findings.

Autor 1:  Gustavo de Souza VIEIRA

E-mail 1:  [email protected]

Autor 2:   João Figueira SCARINI

E-mail 2:  [email protected]

Autor 3 :  Sheila Tiemi NAGAMATSU

E-mail 3:  [email protected]

Autor 4:  Alfio Jose TINCANI

E-mail 4:  [email protected]

Autor 5:  Carlos Takahiro CHONE

E-mail 5:  [email protected]

Autor 6:  Adriana Franco PAES LEME

E-mail 6:  [email protected]

Autor 7:  Fernanda Viviane MARIANO

E-mail 7:  [email protected]