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一种铜死亡多组学预后模型影响胃腺癌的预后。

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

作者信息

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

机构信息

Department of Medical Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.

出版信息

Clin Epigenetics. 2025 Jun 12;17(1):99. doi: 10.1186/s13148-025-01894-0.

DOI:10.1186/s13148-025-01894-0
PMID:40506764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12160351/
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.

摘要

背景

铜死亡是一种与铜离子相关的细胞死亡形式，已被证明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死亡相关基因的作用，有助于加深我们对疾病机制的理解，并改善预后预测。

目的

本研究旨在从多组学角度阐明铜死亡相关基因在胃癌中的作用。

材料与方法

我们利用来自TCGA和GEO数据库的多组学测序数据，探索铜死亡基因与胃癌发生、临床表型及预后之间的关系。该分析涵盖了突变、拷贝数变异、甲基化、mRNA表达、可变剪接和APA改变。此外，我们还通过ceRNA相互作用、基因突变和DNA甲基化研究了铜死亡基因在胃癌中的调控作用。随后构建了胃癌的多组学预后模型。

结果

我们的研究结果显示，CDKN2A是胃癌中最常发生突变的基因。铜死亡基因的总体突变和PDHB的拷贝数改变显著影响胃癌预后。CDKN2A的甲基化、可变剪接和APA改变也会影响患者的预后。值得注意的是，发现铜死亡中的关键基因MTF1会影响胃癌细胞系的凋亡和侵袭。

结论

我们成功开发了一种胃癌多组学预后模型，对患者预后具有重要的预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1802/12160351/08e928e5a22f/13148_2025_1894_Fig10_HTML.jpg
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