Integrated Analysis of Multi-Omics Data to Establish a Hypoxia-Related Prognostic Model in Osteosarcoma.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-10-26 eCollection Date: 2022-01-01 DOI:10.1177/11769343221128537
Ye Tong, Xiaoqing Zhang, Ye Zhou
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Abstract

Background: Osteosarcoma (OS) is the most common malignant bone tumor in clinical practice, and currently, the ability to predict prognosis in the diagnosis of OS is limited. There is an urgent need to find new diagnostic methods and treatment strategies for OS.

Material and methods: We downloaded the multi-omics data for OS from the TARGET database. Prognosis-associated methylation sites were used to identify clustered subtypes of OS, and OS was classified into 3 subtypes (C1, C2, C3). Survival analysis showed significant differences between the C3 subtype and the other subtypes. Subsequently, differentially expressed genes (DEGs) across subtypes were screened and subjected to pathway enrichment analysis.

Results: A total of 249 DEGs were screened from C3 subtype to other subtypes. Metabolic pathway enrichment analysis showed that DEGs were significantly enriched to the hypoxic pathway. Based on univariate and multivariate COX regression analysis, 12 genes from the hypoxia pathway were further screened and used to construct hypoxia-related prognostic model (HRPM). External validation of the HRPM was performed on the GSE21257 dataset. Finally, differences in survival and immune infiltration between high and low risk score groups were compared.

Conclusion: In summary, we proposed a hypoxia-associated risk model based on a 12-gene expression signature, which is potentially valuable for prognostic diagnosis of patients with OS.

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多组学数据综合分析建立骨肉瘤缺氧相关预后模型。
背景:骨肉瘤(Osteosarcoma, OS)是临床最常见的恶性骨肿瘤,目前在骨肉瘤的诊断中预测预后的能力有限。目前迫切需要寻找新的诊断方法和治疗策略。材料与方法:从TARGET数据库中下载OS的多组学数据。预后相关的甲基化位点被用来鉴定OS的聚集亚型,并将OS分为3个亚型(C1, C2, C3)。生存分析显示C3亚型与其他亚型之间存在显著差异。随后,筛选不同亚型的差异表达基因(DEGs)并进行途径富集分析。结果:从C3亚型到其他亚型共筛选出249例deg。代谢途径富集分析表明,DEGs显著富集于缺氧途径。通过单因素和多因素COX回归分析,进一步筛选出12个缺氧通路基因,构建缺氧相关预后模型(HRPM)。在GSE21257数据集上对HRPM进行外部验证。最后比较高、低风险评分组生存率和免疫浸润的差异。结论:综上所述,我们提出了一个基于12个基因表达特征的缺氧相关风险模型,该模型对OS患者的预后诊断具有潜在价值。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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