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

## TL;DR

High levels of the MAP4K4 gene predict worse outcomes in a specific type of gastric cancer called microsatellite instability gastric cancer.

## Contribution

MAP4K4 is identified as a novel prognostic marker specifically for microsatellite instability gastric cancer.

## Key findings

- High MAP4K4 expression is linked to poor survival in microsatellite instability gastric cancer.
- MAP4K4high tumors show increased extracellular matrix remodeling and immune cell infiltration.
- MAP4K4high tumors with a CIN-like phenotype have particularly poor outcomes.

## Abstract

This study identifies the high expression of MAP4K4 as a biomarker of poor prognosis in microsatellite instability gastric cancer. MAP4K4’s prognostic significance was specific to MSI-GC than other molecular GC subtypes. Further analysis revealed that tumors with high MAP4K4 expression exhibit enhanced extracellular matrix remodeling, epithelial–mesenchymal transition, and distinct immune microenvironment characteristics, such as increased monocyte and CAF infiltration. These findings position MAP4K4 as a promising marker for risk stratification and a potential therapeutic target in MSI-GC.

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.