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鉴定缺氧特征以评估卵巢癌患者的肿瘤免疫微环境并预测预后

Identification of Hypoxia Signature to Assess the Tumor Immune Microenvironment and Predict Prognosis in Patients with Ovarian Cancer.

作者信息

Wei Chunyan, Liu Xiaoqing, Wang Qin, Li Qipei, Xie Min

机构信息

Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Gynaecology and Obstetrics, Maternal and Child Health Hospital of Shangzhou District, Shangluo, Shanxi Province, China.

出版信息

Int J Endocrinol. 2021 Dec 14;2021:4156187. doi: 10.1155/2021/4156187. eCollection 2021.

DOI:10.1155/2021/4156187
PMID:34950205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8692015/
Abstract

BACKGROUND

The 5-year overall survival rate of ovarian cancer (OC) patients is less than 40%. Hypoxia promotes the proliferation of OC cells and leads to the decline of cell immunity. It is crucial to find potential predictors or risk model related to OC prognosis. This study aimed at establishing the hypoxia-associated gene signature to assess tumor immune microenvironment and predicting the prognosis of OC.

METHODS

The gene expression data of 378 OC patients and 370 OC patients were downloaded from datasets. The hypoxia risk model was constructed to reflect the immune microenvironment in OC and predict prognosis.

RESULTS

8 genes (AKAP12, ALDOC, ANGPTL4, CITED2, ISG20, PPP1R15A, PRDX5, and TGFBI) were included in the hypoxic gene signature. Patients in the high hypoxia risk group showed worse survival. Hypoxia signature significantly related to clinical features and may serve as an independent prognostic factor for OC patients. 2 types of immune cells, plasmacytoid dendritic cell and regulatory T cell, showed a significant infiltration in the tissues of the high hypoxia risk group patients. Most of the immunosuppressive genes (such as ARG1, CD160, CD244, CXCL12, DNMT1, and HAVCR1) and immune checkpoints (such as CD80, CTLA4, and CD274) were upregulated in the high hypoxia risk group. Gene sets related to the high hypoxia risk group were associated with signaling pathways of cell cycle, MAPK, mTOR, PI3K-Akt, VEGF, and AMPK.

CONCLUSION

The hypoxia risk model could serve as an independent prognostic indicator and reflect overall immune response intensity in the OC microenvironment.

摘要

背景

卵巢癌(OC)患者的5年总生存率低于40%。缺氧促进OC细胞增殖并导致细胞免疫功能下降。寻找与OC预后相关的潜在预测指标或风险模型至关重要。本研究旨在建立缺氧相关基因特征以评估肿瘤免疫微环境并预测OC的预后。

方法

从数据集中下载了378例OC患者和370例OC患者的基因表达数据。构建缺氧风险模型以反映OC中的免疫微环境并预测预后。

结果

缺氧基因特征包括8个基因(AKAP12、ALDOC、ANGPTL4、CITED2、ISG20、PPP1R15A、PRDX5和TGFBI)。高缺氧风险组患者的生存率较差。缺氧特征与临床特征显著相关,可能作为OC患者的独立预后因素。2种免疫细胞,浆细胞样树突状细胞和调节性T细胞,在高缺氧风险组患者的组织中显示出显著浸润。大多数免疫抑制基因(如ARG1、CD160、CD244、CXCL12、DNMT1和HAVCR1)和免疫检查点(如CD80、CTLA4和CD274)在高缺氧风险组中上调。与高缺氧风险组相关的基因集与细胞周期、MAPK、mTOR、PI3K-Akt、VEGF和AMPK的信号通路相关。

结论

缺氧风险模型可作为独立的预后指标,并反映OC微环境中的整体免疫反应强度。

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