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

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-06-05 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S499695

Hui Liu, Yongming Huang, Guanghua Fu, Bo Lei, Ke Liu

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引用次数: 0

Abstract

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.

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IGFBP1是预测胃癌无复发生存的10个代谢因子之一，并通过ZFX-IGFBP1轴促进癌症进展。

导读：代谢相关基因（MRGs）对癌症预后有重要影响，但它们在胃癌（GC）中的作用尚不清楚。方法：我们分析了407例TCGA胃癌患者的24,991个基因，以确定基于代谢基因的预后特征。体外和体内功能实验验证了关键发现，而通过启动子相互作用分析探索转录调节机制。结果：一个强大的10代谢基因标记被确定为胃癌无复发生存（RFS）的强烈预测。胰岛素样生长因子结合蛋白1 （IGFBP1）表达升高与总生存期和无病生存期降低相关。功能研究表明IGFBP1在促进胃癌增殖和转移中具有致癌作用。从机制上讲，锌指蛋白X-linked （ZFX）通过直接结合IGFBP1的启动子来激活其转录。讨论：我们建立了一个整合10个代谢基因特征的预测图，用于GC RFS预测。IGFBP1作为潜在的治疗靶点和生物标志物出现，zfx驱动的转录激活是GC进展的一个新的调控轴。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.