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机器学习分析与卵巢癌特定基因筛选相关的氧化应激表型。

Machine learning analysis of oxidative stress-related phenotypes for specific gene screening in ovarian cancer.

机构信息

Department of Women's Oncology, Shuangyu Campus, Wenzhou Central Hospital, Wenzhou, Zhejiang, China.

出版信息

Environ Toxicol. 2024 Oct;39(10):4763-4775. doi: 10.1002/tox.24321. Epub 2024 Aug 20.

Abstract

BACKGROUND

Oxidative stress serves a crucial role in tumor development. However, the relationship between ovarian cancer and oxidative stress remains unknown. We aimed to create an oxidative stress-related prognostic signature to enhance the prognosis prediction of CC patients using bioinformatics.

METHODS

The genes differentially expressed and associated with oxidative stress were extracted with the help of "limma" packages. The model for prognosis was created using Multivariate Cox regression analysis to determine the risk related to the genes related to oxidative stress. Patients were categorized as low-risk or high-risk based on the median score. The receiver operation characteristic (ROC) and survival curves were used to evaluate the predictive effect of the prognostic signature. We utilized quantitative real-time PCR to assess the expression levels of key genes associated with oxidative stress in ovarian cancer cell lines (SKOV3, OVCAR3, and HeyA8) and normal ovarian epithelial cells (HOSEpiC).

RESULTS

A signature comprising seven genes associated with oxidative stress was developed to prognosticate patients with ovarian cancer. Overall survival (OS) of the patient having CC was determined using Kaplan-Meier analysis. It was found that patient with a higher risk score had lower OS than the low-risk score. The signature of genes associated with oxidative stress was found to be independently prognostic for 1, 2, and 3 years. Further research found that the expression levels of nine hub genes had a strong association with patient outcomes. Our analysis revealed a higher expression of CX3CR1 in ovarian cancer cell lines compared with normal cells.

CONCLUSIONS

To deploy a novel oxidative stress-related prognostic signature as an independent biomarker in cervical cancer, we developed and validated it.

摘要

背景

氧化应激在肿瘤发展中起着至关重要的作用。然而,卵巢癌与氧化应激之间的关系尚不清楚。我们旨在利用生物信息学创建与氧化应激相关的预后特征,以增强 CC 患者的预后预测。

方法

借助“limma”包提取差异表达并与氧化应激相关的基因。使用多变量 Cox 回归分析创建用于预后的模型,以确定与氧化应激相关基因的风险。根据中位数评分将患者分为低风险或高风险。使用接收者操作特征(ROC)和生存曲线评估预后特征的预测效果。我们利用定量实时 PCR 评估卵巢癌细胞系(SKOV3、OVCAR3 和 HeyA8)和正常卵巢上皮细胞(HOSEpiC)中与氧化应激相关的关键基因的表达水平。

结果

开发了一个由七个与氧化应激相关的基因组成的signature 来预测卵巢癌患者的预后。使用 Kaplan-Meier 分析确定具有 CC 的患者的总体生存率(OS)。结果发现,风险评分较高的患者的 OS 低于低风险评分的患者。与氧化应激相关的基因signature 被发现对 1、2 和 3 年的预后具有独立预测作用。进一步的研究发现,九个枢纽基因的表达水平与患者的预后有很强的关联。我们的分析表明,CX3CR1 在卵巢癌细胞系中的表达高于正常细胞。

结论

为了将一种新的与氧化应激相关的预后特征作为宫颈癌的独立生物标志物进行部署,我们对其进行了开发和验证。

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