Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing’s sarcoma
Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing’s sarcoma
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ICAM1 失活可抑制尤文氏肉瘤的转移并改善预后
DOI：
10.1007/s00432-020-03431-3
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发表时间：
2020
影响因子：
3.6
通讯作者：
Kaijin Guo
中科院分区：
文献类型：
--
作者：
Bin Pan;Xiangbo Bu;Menghan Cao;Xin Zhang;Tianqun Huo;Ziang Li;Xiao Gao;Li Jing;Xuanxiang Luo;Hu Feng;Feng Yuan;Kaijin Guo
研究背景：尤文氏肉瘤（ES）是一种恶性肿瘤，好发于长骨、骨盆等骨组织以及部分软组织。常发生于儿童和青少年，仅次于骨肉瘤和横纹肌肉瘤。近30年来，ES转移的基因组机制研究进展甚微。方法：将ES转移样本与原发肿瘤样本的基因表达序列进行比较，获得差异表达基因（DEGs）。随后，我们注释了 DEG 的基因功能和富集途径。此外，还构建了蛋白质和蛋白质相互作用网络来筛选导致ES转移的关键基因。然后，进行细胞和分子生物学实验来验证生物信息学分析的结果。最后，我们评估了关键基因EWSR和FLI1之间表达的相关性，并对ICAM1进行了生存分析。结果：我们的研究揭示了153个DEG。其中，82个（53.59%）上调，其余71个（46.41%）下调。生物信息学分析表明ICAM1是导致ES侵袭和转移的关键基因。通过细胞生物学和分子生物学实验，ICAM1失活抑制了ES细胞的转移。生存和相关分析显示ICAM1是ES患者的危险因素，并且ICAM1表达与EWSR和FLI1表达相关。结论：我们的研究表明ICAM1失活可抑制ES的转移并改善其预后。此外，我们的研究结果使人们更好地了解转移性 ES 的潜在机制，为 ES 患者的准确诊断和治疗靶点奠定了基础。
Background：Ewing’s sarcoma (ES) is a kind of malignant tumor, which often occurs in the long bone, pelvis, and other bone tissues, as well as some soft tissues. It often occurs in children and adolescents, second only to osteosarcoma and rhabdomyosarcoma. In the past 30 years, little progress has been made on the genomic mechanism of ES metastasis. Methods：The gene expression sequence of ES metastasis samples was compared with that of primary tumor samples to obtain differentially expressed genes (DEGs). Subsequently, we annotated the gene functions and enriched pathways of DEGs. Additionally, the protein and protein interaction network were constructed to screen key genes that can lead to the metastasis in ES. Then, cell and molecular biology experiments were conducted to verify the results obtained from the bioinformatics analysis. Finally, we assessed the correlation of expression between the key genes EWSR and FLI1, and conducted a survival analysis of ICAM1.Results：Our study revealed 153 DEGs. Of these, 82 (53.59%) were upregulated and the remaining 71 (46.41%) were downregulated. The bioinformatics analysis showed that ICAM1 was the key gene leading to the invasion and metastasis of ES. Through cell biology and molecular biology experiments, inactivation of ICAM1 inhibited the metastasis of ES cells. The survival and correlation analyses showed that ICAM1 was a risk factor in patients with ES, and that ICAM1 expression was correlated with EWSR and FLI1 expression. Conclusion：Our study shows that inactivation of ICAM1 inhibits metastasis and improves the prognosis of ES. Additionally, our findings provide a better understanding of the underlying mechanisms of metastatic ES, a basis for an accurate diagnosis, and therapeutic targets for ES patients.