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CD44表达与骨肉瘤细胞进展和免疫浸润相关,并影响Wnt/β-连环蛋白信号通路。

CD44 expression is correlated with osteosarcoma cell progression and immune infiltration and affects the Wnt/β-catenin signaling pathway.

作者信息

Ji Hairu, Kong Lingwei, Wang Yu, Hou Zhiping, Kong Wei, Qi Jiemin, Jin Yu

机构信息

Department of Pathology, Chengde Medical University, Chengde 067000, China.

Department of Traumatology and Orthopaedics, Affiliated Hospital of Chengde Medical University, Chengde 067000, China.

出版信息

J Bone Oncol. 2023 May 25;41:100487. doi: 10.1016/j.jbo.2023.100487. eCollection 2023 Aug.

Abstract

CD44 is associated with a variety of human diseases and plays a potential role in tumorigenesis, however, the mechanism of its role in osteosarcoma remains unclear. We analyzed the expression of CD44 in the Cancer Genome Atlas (TCGA) and genotype-tissue expression pan-cancer data and found that it was highly expressed in most tumors, including sarcoma. The expression of CD44 in osteosarcoma cell lines was higher than that in human osteoblast cell line in the results of the Western blot and Immunohistochemical staining assay. The results of colony formation assay and CCK 8 showed that CD44 improved the proliferation capacity of osteosarcoma cells, transwell assay and wound healing assay showed that CD44 improved the migration capacity of osteosarcoma cells. Further studies revealed that CD44 exerts its influence on the biological behavior of osteosarcoma cells through the Wnt/β-catenin signaling pathway. Since CD44 may be involved in the immune response, we analyzed the correlation between CD44 expression and immune cell infiltration in TCGA database using the previous cluster analyzer R software package, TIMER2.0 database and, GEPIA2 database, and found its involvement in the immune infiltration of osteosarcoma. Therefore, we believe that CD44 could be a potential target for the treatment of osteosarcoma patients and may be a candidate biomarker for immune infiltration-related prognosis.

摘要

CD44与多种人类疾病相关,并在肿瘤发生中发挥潜在作用,然而,其在骨肉瘤中作用的机制仍不清楚。我们分析了癌症基因组图谱(TCGA)和基因型-组织表达泛癌数据中CD44的表达情况,发现它在包括肉瘤在内的大多数肿瘤中高表达。蛋白质免疫印迹和免疫组织化学染色分析结果显示,CD44在骨肉瘤细胞系中的表达高于人成骨细胞系。集落形成实验和CCK-8实验结果表明,CD44提高了骨肉瘤细胞的增殖能力,Transwell实验和伤口愈合实验表明,CD44提高了骨肉瘤细胞的迁移能力。进一步研究表明,CD44通过Wnt/β-连环蛋白信号通路对骨肉瘤细胞的生物学行为产生影响。由于CD44可能参与免疫反应,我们使用之前的聚类分析软件包R、TIMER2.0数据库和GEPIA2数据库分析了TCGA数据库中CD44表达与免疫细胞浸润之间的相关性,发现其参与了骨肉瘤的免疫浸润。因此,我们认为CD44可能是骨肉瘤患者治疗的潜在靶点,并且可能是免疫浸润相关预后的候选生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d0a/10242553/95655d5fa63f/gr1.jpg

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