Autor(es)

Ortiz, Alvaro De Jesus Huamani ; Segura, Anthony Vladimir Campos ; Bocanegra, Kevin Jorge Magano ; Sotomayor, Mariana Belen Velasquez ; Pastor, Heli Jaime Barron ; de Barron, Yesica Barron Llimpe Mitma ; Villanueva, Ruy Diego Chacon ; Carrasco, Alexis German Murillo ; Rojas, Cesar Alexander Ortiz

• Tipo de documento: Artigo Científico
• Fonte: CANCERS; v. 17, n. 3, p. 16-pg., 2025-02-01.

Resumo

Background/Objectives: Gastric cancer (GC) is a highly aggressive malignancy with diverse molecular subtypes. While microsatellite instability (MSI) GC generally carries a favorable prognosis, a subset of patients experiences poor outcomes, highlighting the need for refined prognostic markers. Methods: This study utilized transcriptomic and clinical data from two independent cohorts, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), to identify novel prognostic genes in MSI-GC. Results: Through rigorous survival analysis, we identified high MAP4K4 expression (MAP4K4high) as an independent and robust predictor of poor overall survival (OS) and disease-free survival (DFS) specifically within the MSI-GC subtype. MAP4K4high was associated with increased hazard ratios for both OS and DFS in both cohorts, even after adjusting for clinicopathological factors. Further analysis revealed that MAP4K4high MSI-GC tumors exhibit a distinct molecular profile characterized by increased extracellular matrix remodeling, epithelial-mesenchymal transition, and a microenvironment enriched in monocytes and cancer-associated fibroblasts (CAFs). Notably, a subgroup of MSI-GC patients with a CIN-like phenotype and high MAP4K4 expression exhibited particularly dismal outcomes. Conclusions: Our findings establish MAP4K4 as a promising prognostic biomarker for risk stratification in MSI-GC and suggest its potential role in driving aggressive tumor behavior through modulation of the tumor microenvironment. (AU)

• Processo FAPESP: 19/05583-0 - Enriquecimento de microvesículas extracelulares STn/Tn+ derivadas de tumor para avaliar marcadores baseados em miRNA em pacientes com Câncer de Mama
• Beneficiário: Alexis Germán Murillo Carrasco
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/08430-5 - Deteção dos transcritos do gene TP73 na Leucemia Promielocítica Aguda e seu impacto no prognóstico e resposta terapêutica
• Beneficiário: César Alexander Ortiz Rojas
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto