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基于生物信息学的铁死亡相关基因对胃癌的预后影响

Bioinformatics-based Prognosis Effect of Ferroptosis-related Genes on Gastric Cancer.

作者信息

Wang Tao, Zeng Aoran, Zhu Lili, Liu Fengzhi, Pang Bowen, Liu Yan, Liu Zijian, Wang Jing

机构信息

Department of Ultrasound, The second affiliated Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang, China.

Department of Biology, School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang, Heilongjiang, China.

出版信息

Cell Biochem Biophys. 2025 Jun;83(2):2237-2251. doi: 10.1007/s12013-024-01634-w. Epub 2025 Feb 13.

Abstract

This study investigated the relationship between ferroptosis related genes and the prognosis of gastric cancer patients. Gene expression and corresponding clinical data were obtained from the TCGA database. Differentially expressed genes in gastric cancer were identified using R software, and prognostic-related genes were screened using univariate Cox regression analysis. Prognostic genes related to ferroptosis were determined using a Venn diagram. A prognostic model was constructed using LASSO-Cox regression analysis. Additionally, the expression of DUSP1 in gastric cancer was validated through immunohistochemistry, Western blot, and qRT-PCR. The impact of DUSP1 on ferroptosis was analyzed by measuring iron and lipid content in gastric cancer cell lines. A total of 407 gastric cancer patients were included as the training cohort. Fifteen prognostic genes related to ferroptosis were identified, and an 11-gene prognostic model was constructed. Risk scores were calculated for each patient, revealing that the overall survival rate was higher in the low-risk group compared to the high-risk group. ROC curves, PCA plots, and Kaplan-Meier survival curves demonstrated the model's efficacy in predicting 5-year survival rates (AUC = 0.716). Increased DUSP1 expression, correlated with higher Fe2+ and lipid ROS levels, was observed in gastric cancer cells with increasing Erastin concentration. The prognostic model effectively predicts gastric cancer patient outcomes. DUSP1 is lowly expressed in gastric cancer tissues and is associated with malignancy and metastasis, playing a role in ferroptosis in gastric cancer cells.

摘要

本研究调查了铁死亡相关基因与胃癌患者预后之间的关系。基因表达及相应临床数据来自TCGA数据库。使用R软件鉴定胃癌中差异表达的基因,并通过单变量Cox回归分析筛选与预后相关的基因。使用维恩图确定与铁死亡相关的预后基因。采用LASSO-Cox回归分析构建预后模型。此外,通过免疫组织化学、蛋白质免疫印迹和qRT-PCR验证了胃癌中DUSP1的表达。通过测量胃癌细胞系中的铁和脂质含量,分析了DUSP1对铁死亡的影响。共有407例胃癌患者作为训练队列。鉴定出15个与铁死亡相关的预后基因,并构建了一个11基因的预后模型。计算了每位患者的风险评分,结果显示低风险组的总生存率高于高风险组。ROC曲线、主成分分析图和Kaplan-Meier生存曲线证明了该模型在预测5年生存率方面的有效性(AUC = 0.716)。随着埃拉斯汀浓度的增加,在胃癌细胞中观察到DUSP1表达增加,且与较高的Fe2+和脂质ROS水平相关。该预后模型能够有效预测胃癌患者的预后。DUSP1在胃癌组织中低表达,与恶性肿瘤和转移相关,在胃癌细胞的铁死亡中发挥作用。

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