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基于缺氧基因的signature 预测儿童骨肉瘤的生存并影响肿瘤免疫微环境。

A Hypoxia Gene-Based Signature to Predict the Survival and Affect the Tumor Immune Microenvironment of Osteosarcoma in Children.

机构信息

Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.

出版信息

J Immunol Res. 2021 Jul 15;2021:5523832. doi: 10.1155/2021/5523832. eCollection 2021.

Abstract

Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.

摘要

骨肉瘤是一种快速发展的恶性骨肿瘤,预后不良。在骨肉瘤中,缺氧促进恶性表型,导致一系列免疫抑制过程、预后不良和高转移风险。然而,肿瘤微环境中高氧的研究还需要更多的分析方法。我们从治疗性应用研究以产生有效的治疗(TARGET)数据库中获得了 88 名骨肉瘤患儿患者和 53 名 RNA 序列和临床病理数据的患儿患者来自基因表达综合数据库(GEO)。我们开发了一个与缺氧相关的四个基因特征来反映骨肉瘤中的免疫微环境,预测生存率。高风险评分表明预后不良和免疫抑制微环境。存在与缺氧相关的四个基因特征与临床和分子特征相关,是骨肉瘤患儿的重要预后预测因子。总之,我们建立并验证了一个与缺氧相关的四个基因特征来预测恢复,并提出了一个独立的预后预测因子,代表骨肉瘤微环境中整体免疫反应强度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b39b/8299210/0a813a366ed6/JIR2021-5523832.001.jpg

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