Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing's sarcoma

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ORIGINAL ARTICLE – CANCER RESEARCH

Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing’s sarcoma Bin Pan1 · Xiangbo Bu1 · Menghan Cao2 · Xin Zhang3,4 · Tianqun Huo1 · Ziang Li1 · Xiao Gao1 · Li Jing1 · Xuanxiang Luo1 · Hu Feng1 · Feng Yuan1 · Kaijin Guo1  Received: 21 April 2020 / Accepted: 19 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

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. Keywords  Ewing’s sarcoma · Bioinformatics · ICAM1 · Metastasis Bin Pan, Xiangbo Bu and Menghan Cao should be considered as joint first authors. * Hu Feng [email protected] * Feng Yuan [email protected] * Kaijin Guo [email protected] 1



Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China

2



Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China

3

Department of Dermatology, Xuzhou Children’s Hospital, Xuzhou Medical University, Xuzhou 221000, China

4

Department of Dermatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China



Introduction Ewing’s sarcoma (ES) is a low-grade, high-metastasis skeletal and soft tissue malignancy. Patients with Ewing’s sarcoma have a 5-year survival rate approaching 70% after combined treatment (Gas