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用于预测上皮性卵巢癌患者预后的铜稳态相关基因特征的鉴定

Identification of Copper Homeostasis-Related Gene Signature for Predicting Prognosis in Patients with Epithelial Ovarian Cancer.

作者信息

Yan Ping, Tian Yueqin, Li Xiaojing, Li Shuangmei, Wu Haidong, Wang Tong

机构信息

Department of General Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Cancer Inform. 2024 Aug 13;23:11769351241272400. doi: 10.1177/11769351241272400. eCollection 2024.

Abstract

OBJECTIVES

This research aims to establish a copper homeostasis-related gene signature for predicting the prognosis of epithelial ovarian cancer and to investigate its underlying mechanisms.

METHODS

We mainly constructed the copper homeostasis-related gene signature by LASSO regression analysis. Then multiple methods were used to evaluate the independent predictive ability of the model and explored the mechanisms.

RESULTS

The 15-copper homeostasis-related gene (15-CHRG) signature was successfully established. Utilizing an optimal cut-off value of 0.35, we divided the training dataset into high-risk and low-risk subgroups. Kaplan-Meier analysis revealed that survival times for the high-risk subgroup were significantly shorter than those in the low-risk group (P < .05). Additionally, the Area Under the Curve (AUC) of the 15-CHRG signature achieved 0.822 at 1 year, 0.762 at 3 years, and 0.696 at 5 years in the training set. COX regression analysis confirmed the 15-CHRG signature as both accurate and independent. Gene set enrichment (GSEA), Kyoto Encyclopedia of Gene and Genome (KEGG) and Gene Ontology (GO) analysis showed that there were significant differences in apoptosis, p53 pathway, protein synthesis, hydrolase and transport-related pathways between high-risk group and low-risk group. In tumor immune cell (TIC) analysis, the increased expression of resting mast cells was positively correlated with the risk score.

CONCLUSION

Consequently, the 15-CHRG signature shows significant potential as a method for accurately predicting clinical outcomes and treatment responses in patients with epithelial ovarian cancer.

摘要

目的

本研究旨在建立一种与铜稳态相关的基因特征,用于预测上皮性卵巢癌的预后,并探讨其潜在机制。

方法

我们主要通过LASSO回归分析构建与铜稳态相关的基因特征。然后使用多种方法评估该模型的独立预测能力并探索其机制。

结果

成功建立了包含15个与铜稳态相关基因(15-CHRG)的特征。利用最佳截断值0.35,我们将训练数据集分为高风险和低风险亚组。Kaplan-Meier分析显示,高风险亚组的生存时间明显短于低风险组(P < 0.05)。此外,在训练集中,15-CHRG特征在1年时的曲线下面积(AUC)为0.822,3年时为0.762,5年时为0.696。COX回归分析证实15-CHRG特征既准确又独立。基因集富集(GSEA)、京都基因与基因组百科全书(KEGG)和基因本体论(GO)分析表明,高风险组和低风险组在凋亡、p53通路、蛋白质合成、水解酶和转运相关通路方面存在显著差异。在肿瘤免疫细胞(TIC)分析中,静息肥大细胞表达的增加与风险评分呈正相关。

结论

因此,15-CHRG特征作为一种准确预测上皮性卵巢癌患者临床结局和治疗反应的方法具有显著潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28b5/11320685/9cef6f4f0e3f/10.1177_11769351241272400-fig1.jpg

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