Transcriptome-Based Survival Analysis Identifies MAP4K4 as a Prognostic Marker in Gastric Cancer with Microsatellite Instability

Huamani Ortiz A.D.J.; Campos Segura A.V.; Magaño Bocanegra K.J.; Velásquez Sotomayor M.B.; Barrón Pastor H.J.; Llimpe Mitma de Barrón Y.; Chacón Villanueva R.D.; Murillo Carrasco A.G.; Ortiz Rojas C.A. · Cancers (2025) · DOI: 10.3390/cancers17030412

Resumen

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.

Instituciones: Universidad Nacional Mayor de San Marcos; Universidad Científica del Sur