Hui Liu,1,* Yongming Huang,2,* Guanghua Fu,3 Bo Lei,4 Ke Liu2 

1Department of General Surgery, Wuhan Asia General Hospital, Wuhan, 430056, People’s Republic of China; 2Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, People’s Republic of China; 3Department of Breast and Thyroid Surgery, the second Affiliated Hospital of Hainan Medical University, Haikou, 570311, People’s Republic of China; 4Department of Gastrointestinal Surgery, Qianjiang Central Hospital, Qianjiang, 433100, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ke Liu, Email unionliuke@163.com Bo Lei, Email 1260849426@qq.com

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.

Keywords: nomogram, metabolic gene, gastric carcinoma, IGFBP1, ZFX