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一种用于预测骨肉瘤预后和评估免疫微环境的端粒相关特征。

A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma.

作者信息

Li Shihao, Zhang Lina, Zhang Haiyang

机构信息

Department of Orthopedics, Zibo Central Hospital West Campus, Zibo, China.

Department of Hand and Foot Surgery, Zibo Central Hospital, Zibo, China.

出版信息

Front Pharmacol. 2025 Jan 27;15:1532610. doi: 10.3389/fphar.2024.1532610. eCollection 2024.

Abstract

OBJECTIVE

Osteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.

METHODS

The data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.

RESULTS

Based on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.

CONCLUSION

A telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.

摘要

目的

骨肉瘤是最常见的原发性骨癌,具有较高的局部侵袭和转移倾向。越来越多的研究表明,端粒在癌症的发生和发展中起重要作用。因此,我们在骨肉瘤中建立了一个与端粒相关的特征,以全面评估端粒在该疾病中的致病作用。

方法

从TARGET和基因表达综合数据库收集骨肉瘤数据。首先,我们使用单变量和LASSO Cox回归分析构建了一个与端粒相关的特征。随后,我们通过综合生物信息学分析,分析了骨肉瘤中端粒相关特征的预后价值、功能注释、免疫微环境和细胞通讯模式。使用CCK-8试验分析细胞增殖,使用Transwell试验评估细胞迁移和侵袭能力。

结果

基于SP110、HHAT、TUBB、MORC4、TERT、PPARG、MAP3K5、PAGE5、MAP7和CAMK1G,在骨肉瘤患者中建立了一个与端粒相关的特征。端粒相关特征可以有效预测骨肉瘤患者的预后。高TELscore组的骨肉瘤患者预后较差。此外,端粒相关特征对骨肉瘤的免疫微环境和药物敏感性具有预测价值。最后,我们发现骨肉瘤细胞中MAP7表达显著降低,MAP7表达低的患者预后较差。此外,MAP7的过表达显著降低了骨肉瘤细胞的增殖、细胞迁移和侵袭能力。

结论

在骨肉瘤患者中构建了一个与端粒相关的特征,为预后、免疫微环境和药物敏感性提供了预测价值。此外,MAP7可能作为骨肉瘤患者的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a41/11841432/ea4d122f3888/fphar-15-1532610-g001.jpg

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