Identification of ARAP3 as a regulator of tumor progression, macrophage infiltration and osteoclast differentiation in a tumor microenvironment-related prognostic model of Ewing sarcoma.
Identification of ARAP3 as a regulator of tumor progression, macrophage infiltration and osteoclast differentiation in a tumor microenvironment-related prognostic model of Ewing sarcoma.
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发表时间：
2023
影响因子：
5.3
通讯作者：
Yao Wang;Runyi Jiang;Ting Wang;Zhipeng Wu;Haiyi Gong;Xiaopan Cai;Jialiang Liu;Xing-hai Yang;Haifeng Wei;Jian Jiao;Q. Jia;Cheng Yang;Chenglong Zhao;Jianru Xiao
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文献类型：
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作者：
Yao Wang;Runyi Jiang;Ting Wang;Zhipeng Wu;Haiyi Gong;Xiaopan Cai;Jialiang Liu;Xing-hai Yang;Haifeng Wei;Jian Jiao;Q. Jia;Cheng Yang;Chenglong Zhao;Jianru Xiao
了解尤文肉瘤(ES)肿瘤微环境(TME)的特异性和复杂性，对于识别ES的免疫特性、提高免疫治疗效果的预测、促进治疗靶点的发现具有重要意义。在本研究中，我们不仅基于ES的转录组数据，使用Estimate和WGCNA算法对ES中与TME相关的基因集进行评估，而且还使用单变量Cox回归和Lasso回归构建了一个预后模型(ES评分)，并评估了其对免疫细胞浸润的预测能力。随后，我们确定ARAP3是影响ES细胞TME的关键基因。此外，生物信息学分析和体外实验证明，ARAP3的高表达通过P53信号通路调节ES细胞的增殖、迁移和凋亡，并通过调节肿瘤细胞分泌IL1B和IL11来影响巨噬细胞的侵袭和破骨细胞的分化。
Understanding the specificity and complexity of the tumor microenvironment (TME) of Ewing sarcoma (ES) is essential for identifying the immune characteristics of ES, improving the prediction of immunotherapeutic response, and facilitating therapeutic target discovery. In this study, we not only evaluated the gene sets associated with TME in ES using ESTIMATE and WGCNA algorithms based on the transcriptome data of ES, but also constructed a prognostic model (ES Score) using univariate Cox regression and Lasso regression and assessed its predictive ability on immune cell infiltration. Subsequently, we identified ARAP3 as a key gene affecting the TME of ES. In addition, bioinformatic analyses and in vitro experiments proved that the high expression of ARAP3 regulated ES cell proliferation, migration, as well as apoptosis via the p53 signaling pathway and affected macrophage infiltration and osteoclast differentiation through regulating IL1B and IL11 secretion of tumor cells.