卵巢癌缺氧相关预后模型的建立与验证。

IF 2.5 4区 医学 Q3 ONCOLOGY
Linling Xie, Meijun Pan, Zhaoping Zhang, Xiaotao Jiang, Yi Chen, Guantong Liu, Yanfen Chen, Yuhua Zeng, Jieshan Guan, Ruling Lu, Lei Zeng
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引用次数: 0

摘要

背景:卵巢癌的高异质性给其早期诊断和预后预测带来很大困难。目前迫切需要建立一种基于临床病理特征和基因组学的卵巢癌预后模型。方法:通过癌症基因组图谱(TCGA)和正常组织的基因型-组织表达(GTEx),鉴定OC组织与缺氧相关的差异表达基因(DEGs)。采用LASSO Cox回归分析在TCGA-GTEx队列中建立预后模型,并在GEO-OC队列中验证其预测价值。功能富集分析探讨了潜在的机制。通过构建SKOV3细胞系缺氧模型,并应用qRT-PCR技术,研究缺氧与预后模型中两个新基因(ISG20和ANGPTL4)的关系。结果:共鉴定出12例与预后缺氧相关的deg,选取其中9例建立预后模型。将OC患者分为两个危险组,经生存分析,高危组的生存时间比低危组短。单因素和多因素Cox回归分析表明,风险评分是影响总生存的独立危险因素。已确定的预后低氧相关基因标记的生物学功能与免疫细胞浸润有关。ISG20在cocl2模拟缺氧的SKOV3细胞系中低表达,与HIF-1α呈负相关。结论:我们的研究结果表明,这种与缺氧相关的基因标记可以作为一种令人满意的OC预后分类器,并将有助于研究和开发靶向治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development and Validation of a Hypoxia-related Prognostic Model for Ovarian Cancer.

Background: The high heterogeneity of ovarian cancer (OC) brings great difficulties to its early diagnosis and prognostic forecast. There is an urgent need to establish a prognostic model of OC based on clinicopathological features and genomics.

Methods: We identified hypoxia-related differentially expressed genes (DEGs) between OC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression (GTEx). LASSO Cox regression analysis was applied for building a prognostic model in the TCGA-GTEx cohorts, and its predictive value was validated in the GEO-OC cohort. Functional enrichment analysis was performed to investigate the underlying mechanisms. By constructing a hypoxia model of the SKOV3 cell line and applying qRT-PCR, we investigated the relationship between hypoxia with two novel genes in the prognostic model (ISG20 and ANGPTL4).

Results: Twelve prognostic hypoxia-related DEGs were identified, and nine of them were selected to establish a prognostic model. OC patients were stratified into two risk groups, and the high-risk group showed reduced survival time compared to the low-risk group upon survival analysis. Univariate and multivariate Cox regression analysis demonstrated that the risk score was an independent risk factor for overall survival. The biological function of the identified prognostic hypoxia-related gene signature was involved in immune cell infiltration. Low expression of ISG20 was observed in the CoCl2-mimicked hypoxic SKOV3 cell line and negatively correlated with HIF-1α.

Conclusion: Our findings showed that this hypoxia-related gene signature could serve as a satisfactory prognostic classifier for OC and will be beneficial to the research and development of targeted therapeutic strategies.

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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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