Wang Yao, Jiang Runyi, Wang Ting, Wu Zhipeng, Gong Haiyi, Cai Xiaopan, Liu Jialiang, Yang Xinghai, Wei Haifeng, Jiao Jian, Jia Qi, Yang Cheng, Zhao Chenglong, Xiao Jianru
Spine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University Shanghai, China.
Am J Cancer Res. 2023 Aug 15;13(8):3721-3740. eCollection 2023.
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.
了解尤因肉瘤（ES）肿瘤微环境（TME）的特异性和复杂性对于识别ES的免疫特征、改善免疫治疗反应预测以及促进治疗靶点发现至关重要。在本研究中，我们不仅基于ES的转录组数据，使用ESTIMATE和WGCNA算法评估了与ES中TME相关的基因集，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的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细胞增殖、迁移以及凋亡，并通过调节肿瘤细胞的IL1B和IL11分泌影响巨噬细胞浸润和破骨细胞分化。
