A multi-omics prognostic model of cuproptosis affects the prognosis of stomach adenocarcinoma.

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2025-06-12 DOI:10.1186/s13148-025-01894-0

Yinying Wu, Yangwei Fan, Xuyuan Dong, Danfeng Dong, Yu Shi, Meichen Wang, Jia Wang, Yuqian Yang, Nan Yang, Fengyun Ou, Enxiao Li

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引用次数: 0

Abstract

Background: Cuproptosis, a form of cell death associated with copper ions, has been linked to the pathogenesis of various cancers, including gastric cancer. Investigating the role of cuproptosis-related genes through multi-omics analysis can enhance our understanding of disease mechanisms and improve prognosis prediction.

Objective: This study aims to elucidate the role of cuproptosis-related genes in gastric cancer from a multi-omics perspective.

Materials and methods: We utilized multi-omics sequencing data from TCGA and GEO databases to explore the relationships between cuproptosis genes and gastric carcinogenesis, clinical phenotypes, and prognosis. This analysis encompassed mutation, copy number variation, methylation, mRNA expression, alternative splicing, and APA alterations. Additionally, we examined the regulatory roles of cuproptosis genes in gastric cancer through ceRNA interactions, gene mutations, and DNA methylation. A multi-omics prognostic model for gastric cancer was subsequently constructed.

Results: Our findings revealed that CDKN2A was the most frequently mutated gene in gastric cancer. Overall mutations in cuproptosis genes and copy number alterations of PDHB significantly impacted gastric cancer prognosis. Methylation, alternative splicing, and APA alterations of CDKN2A also influenced patient outcomes. Notably, MTF1, a key gene in cuproptosis, was found to affect apoptosis and invasion in gastric cancer cell lines.

Conclusion: We successfully developed a multi-omics prognostic model for gastric cancer that offers significant predictive value for patient outcomes.

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一个多组学预测模型影响胃腺癌的预后。

背景：铜坏死是一种与铜离子相关的细胞死亡形式，与包括胃癌在内的多种癌症的发病机制有关。通过多组学分析研究铜裂相关基因的作用，可以增强我们对疾病机制的认识，改善预后预测。目的：本研究旨在从多组学角度阐明铜裂相关基因在胃癌中的作用。材料和方法：我们利用TCGA和GEO数据库的多组学测序数据，探讨铜质增生基因与胃癌发生、临床表型和预后的关系。该分析包括突变、拷贝数变异、甲基化、mRNA表达、选择性剪接和APA改变。此外，我们通过ceRNA相互作用、基因突变和DNA甲基化研究了铜裂基因在胃癌中的调节作用。随后建立了胃癌多组学预后模型。结果：CDKN2A是胃癌中最常见的突变基因。cuprotosis基因总体突变和PDHB拷贝数改变显著影响胃癌预后。CDKN2A的甲基化、选择性剪接和APA改变也会影响患者的预后。值得注意的是，在胃癌细胞系中，发现了铜质增生的关键基因MTF1影响细胞凋亡和侵袭。结论：我们成功建立了胃癌多组学预后模型，对患者预后具有重要的预测价值。

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

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.