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基于氧化应激反应识别分子亚群并建立风险模型预测肺腺癌患者总生存期。

Identification of molecular subgroups and establishment of risk model based on the response to oxidative stress to predict overall survival of patients with lung adenocarcinoma.

机构信息

Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, 518036, Guangdong, China.

Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China.

出版信息

Eur J Med Res. 2023 Sep 9;28(1):333. doi: 10.1186/s40001-023-01290-5.

Abstract

OBJECTIVE

Oxidative stress is associated with the occurrence and development of lung cancer. However, the specific association between lung cancer and oxidative stress is unclear. This study aimed to investigate the role of oxidative stress in the progression and prognosis of lung adenocarcinoma (LUAD).

METHODS

The gene expression profiles and corresponding clinical information were collected from GEO and TCGA databases. Differentially expressed oxidative stress-related genes (OSRGs) were identified between normal and tumor samples. Consensus clustering was applied to identify oxidative stress-related molecular subgroups. Functional enrichment analysis, GSEA, and GSVA were performed to investigate the potential mechanisms. xCell was used to assess the immune status of the subgroups. A risk model was developed by the LASSO algorithm and validated using TCGA-LUAD, GSE13213, and GSE30219 datasets.

RESULTS

A total of 40 differentially expressed OSRGs and two oxidative stress-associated subgroups were identified. Enrichment analysis revealed that cell cycle-, inflammation- and oxidative stress-related pathways varied significantly in the two subgroups. Furthermore, a risk model was developed and validated based on the OSRGs, and findings indicated that the risk model exhibits good prediction and diagnosis values for LUAD patients.

CONCLUSION

The risk model based on the oxidative stress could act as an effective prognostic tool for LUAD patients. Our findings provided novel genetic biomarkers for prognosis prediction and personalized clinical treatment for LUAD patients.

摘要

目的

氧化应激与肺癌的发生和发展有关。然而,肺癌与氧化应激之间的具体关联尚不清楚。本研究旨在探讨氧化应激在肺腺癌(LUAD)进展和预后中的作用。

方法

从 GEO 和 TCGA 数据库中收集基因表达谱和相应的临床信息。鉴定正常和肿瘤样本之间差异表达的氧化应激相关基因(OSRGs)。应用共识聚类识别氧化应激相关的分子亚群。进行功能富集分析、GSEA 和 GSVA 以研究潜在机制。xCell 用于评估亚组的免疫状态。使用 LASSO 算法开发风险模型,并使用 TCGA-LUAD、GSE13213 和 GSE30219 数据集进行验证。

结果

共鉴定出 40 个差异表达的 OSRGs 和两个与氧化应激相关的亚群。富集分析表明,两个亚组中细胞周期、炎症和氧化应激相关途径存在显著差异。此外,基于 OSRGs 构建并验证了风险模型,结果表明该模型对 LUAD 患者具有良好的预测和诊断价值。

结论

基于氧化应激的风险模型可以作为 LUAD 患者的有效预后工具。我们的研究结果为 LUAD 患者的预后预测和个性化临床治疗提供了新的遗传生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f077/10492289/02eddb97e263/40001_2023_1290_Fig1_HTML.jpg

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