IGFBP1 is One of 10 Metabolic Factors Predicting Recurrence Free Survival in Gastric Cancer and Promotes Cancer Progression via ZFX-IGFBP1 Axis.

INTRODUCTION: Metabolism-related genes (MRGs) critically influence cancer prognosis, yet their role in gastric carcinoma (GC) remains poorly understood. METHODS: We analyzed 24,991 genes from 407 GC patients in TCGA to identify a metabolic gene-based prognostic signature. In vitro and in vivo functional experiments validated key findings, while transcriptional regulation mechanisms were explored through promoter interaction assays. RESULTS: A robust 10-metabolic gene signature was identified as strongly predictive of recurrence-free survival (RFS) in GC. Elevated insulin-like growth factor binding protein 1 (IGFBP1) expression correlated with reduced overall survival and disease-free survival. Functional studies demonstrated IGFBP1's oncogenic role in promoting GC proliferation and metastasis. Mechanistically, zinc finger protein X-linked (ZFX) activated IGFBP1 transcription by directly binding to its promoter. DISCUSSION: We established a prognostic nomogram integrating the 10-metabolic gene signature for GC RFS prediction. IGFBP1 emerges as a potential therapeutic target and biomarker, with ZFX-driven transcriptional activation as a novel regulatory axis in GC progression.