Abstract
<title>Abstract</title> <p> Advanced gastric cancer (GC) shows heterogeneous outcomes, and biomarkers capturing adverse tumor biology and its associated tumor microenvironment (TME) remain undefined. Although tumor-associated macrophages (TAMs) may contribute to tumor progression in GC, the significance of <italic>CSF1R</italic> expression, which regulates macrophage survival, remains unclear. We examined whether <italic>CSF1R</italic> expression identifies a clinically adverse subgroup of advanced GC and characterized the associated TME using whole-transcriptome data from 270 patients in the MONSTAR-SCREEN-2 study. <italic>CSF1R</italic> -high tumors were associated with shorter overall survival than <italic>CSF1R</italic> -low tumors (HR 1.43, P = 0.040), and this association remained significant after multivariable adjustment. Exploratory transcriptomic analyses showed macrophage enrichment, upregulation of TAM-associated genes, enrichment of inflammatory pathways, and higher expression of checkpoint- and T-cell exhaustion-associated transcripts. These findings support CSF1R as a candidate prognostic biomarker that identifies a macrophage-rich TME in advanced GC and warrant external validation and prospective evaluation of TME-modulating strategies in biomarker-defined populations. </p>