研究动态
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基于基底膜基因鉴定 UNC5B 作为骨肉瘤的新型侵袭性生物标志物。

Identification of UNC5B as a novel aggressive biomarker for osteosarcoma based on basement membrane genes.

发表日期:2024 Aug 16
作者: Ruilin Pan, Yiming Zhang, Yanmei Cheng, Zelin Wu, Jin Liu, Zihang Chen, Jinghao Wang, Xiaofang Zhang, Huajun Wang, Shanshan Feng, Xiaofei Zheng
来源: Brain Structure & Function

摘要:

转移性骨肉瘤患者预后较差,基底膜基因(BMGs)的变异与癌症转移相关。然而,BMGs在骨肉瘤中的作用研究甚少。收集BMGs,通过差异分析发现差异表达的BMGs(DE-BMGs)。通过单变量 Cox 回归和 Lasso 回归分析进一步筛选 DE-BMG,鉴定出 6 个关键 BMG,并将其定义为基底膜基因特征 (BMGS)。然后利用BMGS构建骨肉瘤BMGS风险评分系统,根据中位风险评分将骨肉瘤患者分为高危组和低危组。使用单样本基因集富集分析(ssGSEA)和估计评分来研究两个评分组之间免疫浸润的差异。此外,我们通过生物信息学分析研究UNC5B是否影响肿瘤的各种特征,并通过伤口愈合实验、Transwell实验和蛋白质印迹研究UNC5B是否参与骨肉瘤细胞的多种生物学功能。骨肉瘤BMGS风险评分可靠地预测转移风险,患者预后和免疫力。 UNC5B 在骨肉瘤中表达升高,并与免疫浸润、预后和药物敏感性等多种特征相关。体外实验表明,UNC5B敲低降低了骨肉瘤细胞的迁移和侵袭能力以及EMT过程。开发并验证了一种可以有效预测骨肉瘤预后的新型BMGS风险评分系统。该系统中的 UNC5B 基因是骨肉瘤的关键侵袭性生物标志物之一。版权所有 © 2024。由 Elsevier B.V. 出版。
The prognosis of patients with metastatic osteosarcoma is poor, and the variation of basement membrane genes (BMGs) is associated with cancer metastasis. However, the role of BMGs in osteosarcoma has been poorly studied.BMGs were collected and differentially expressed BMGs (DE-BMGs) were found through difference analysis. DE-BMGs were further screened by univariate Cox regression and Lasso regression analyses, and six key BMGs were identified and defined as basement membrane genes signatures (BMGS). Then, BMGS was used to construct the osteosarcoma BMGS risk score system, and the osteosarcoma patients were divided into high- and low-risk groups based on the median risk score. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE scores were used to investigate the differences in immune infiltration between the two scoring groups. Additionally, we investigated whether UNC5B affects various features in tumors by bioinformatic analysis and whether UNC5B was involved in multiple biological functions of osteosarcoma cells by wound healing assay, transwell assay, and western blot.The osteosarcoma BMGS risk score reliably predicts the risk of metastasis, patient prognosis, and immunity. UNC5B expression was elevated in osteosarcoma, and correlated with various characteristics such as immune infiltration, prognosis, and drug sensitivity. In vitro assays showed that UNC5B knockdown reduced osteosarcoma cells' capacity for migration and invasion, and EMT process.A novel BMGS risk score system that can effectively predict the prognosis of osteosarcoma was developed and validated. The UNC5B gene in this system is one of the key aggressive biomarkers of osteosarcoma.Copyright © 2024. Published by Elsevier B.V.