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m6A RNA 甲基化调控因子在骨肉瘤中的潜在作用及其临床预后价值。

Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value.

机构信息

Department of Orthopedics, Haian Hospital of Traditional Chinese Medicine, 55 Ninghai Middle Road, Haian, Nantong, Jiangsu Province, 226600, People's Republic of China.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.

出版信息

J Orthop Surg Res. 2021 May 5;16(1):294. doi: 10.1186/s13018-021-02422-5.

Abstract

BACKGROUND

Osteosarcoma is a disease with high mortality in children and adolescents, and metastasis is one of the important clinical features of osteosarcoma. N6-Methyladenosine (m6A) is the most abundant methylation modification in mRNA, which is regulated by m6A regulators. It is reported that it is related to the occurrence and development of tumors. However, the mechanism of its action in osteosarcoma is rarely known. The purpose of this study was to identify the potential role of m6A regulatory factor in osteosarcoma and its clinical prognostic value.

METHODS

Here, we used The Cancer Genome Atlas (TCGA) to comprehensively analyze the relationship between m6A regulatory factors and osteosarcoma (metastasis group and non-metastasis group). We analyzed their survival relationship and analyzed all the m6A regulatory factors in TCGA tumor data set by using the univariate Cox proportional hazard regression model. Finally, we selected two survival-related methylation regulators (FTO and IGF2BP2) as risk gene signature.

RESULTS

According to the median risk, patients were divided into low-risk group and high-risk group. Multivariate Cox regression analysis showed that these two risk genes were considered to be the key factors independently predicting the prognosis of patients with osteosarcoma. In addition, we verified their characteristics with gene expression omnibus (GEO) DataSets and confirmed that they are related to tumor and immune-related signaling pathways through gene set enrichment analysis (GESA) and immune infiltration analysis.

CONCLUSIONS

In conclusion, m6A regulators might play an important role in the metastasis of osteosarcoma and have potential important value for the prognosis and treatment strategy of osteosarcoma patients.

摘要

背景

骨肉瘤是儿童和青少年中死亡率较高的疾病,转移是骨肉瘤的重要临床特征之一。N6-甲基腺苷(m6A)是 mRNA 中最丰富的甲基化修饰,受 m6A 调节因子调控。据报道,它与肿瘤的发生发展有关。然而,其在骨肉瘤中的作用机制知之甚少。本研究旨在鉴定 m6A 调节因子在骨肉瘤中的潜在作用及其临床预后价值。

方法

在这里,我们使用癌症基因组图谱(TCGA)全面分析 m6A 调节因子与骨肉瘤(转移组和非转移组)之间的关系。我们分析了它们的生存关系,并通过单变量 Cox 比例风险回归模型分析了 TCGA 肿瘤数据集的所有 m6A 调节因子。最后,我们选择了两个与生存相关的甲基化调节因子(FTO 和 IGF2BP2)作为风险基因特征。

结果

根据中位数风险,患者被分为低风险组和高风险组。多变量 Cox 回归分析表明,这两个风险基因被认为是独立预测骨肉瘤患者预后的关键因素。此外,我们通过基因表达综合数据库(GEO)数据集验证了它们的特征,并通过基因集富集分析(GESA)和免疫浸润分析证实它们与肿瘤和免疫相关信号通路有关。

结论

总之,m6A 调节因子可能在骨肉瘤转移中发挥重要作用,对骨肉瘤患者的预后和治疗策略具有潜在的重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e34b/8097785/b3c665d27040/13018_2021_2422_Fig1_HTML.jpg

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