Abstract
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.
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Change history
06 January 2022
A Correction to this paper has been published: https://doi.org/10.1007/s00432-021-03869-z
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Acknowledgements
The present study was supported by the Youth Program of National Natural Science Foundation of China (81801213), China Postdoctoral Science Foundation, No. 65 General Fund (2019M651967), Jiangsu Planned Projects for Postdoctoral Research Funds (2018K176C) and China Postdoctoral start-up fund (2018107007), Science and technology project of yili kazak autonomous prefecture (YZ2019D006). The authors would also like to acknowledge the family and colleagues for giving up their time and energy to support this study.
Funding
The Youth Program of National Natural Science Foundation of China (81801213); China Postdoctoral Science Foundation, No. 65 General Fund (2019M651967); Jiangsu Planned Projects for Postdoctoral Research Funds (2018K176C); China Postdoctoral start-up fund (2018107007); Science and technology project of yili kazak autonomous prefecture (YZ2019D006).
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The original online version of this article was revised due to correction in figure 5.
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Pan, B., Bu, X., Cao, M. et al. Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing's sarcoma. J Cancer Res Clin Oncol 147, 393–401 (2021). https://doi.org/10.1007/s00432-020-03431-3
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DOI: https://doi.org/10.1007/s00432-020-03431-3