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骨肉瘤中新型血管生成相关预后模型的建立及实验验证与免疫浸润特征分析

Development and experimental verification of novel angiogenesis related prognostic model and immune infiltration characterization in osteosarcoma.

作者信息

Ren Shengquan, Pan Rongfang, Wang Zhengdan

机构信息

Department of Hand and Foot Microsurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

出版信息

Discov Oncol. 2024 Sep 5;15(1):411. doi: 10.1007/s12672-024-01292-7.

Abstract

BACKGROUND

As the most common primary bone cancer, osteosarcoma (OS) still lacks satisfactory therapeutic outcomes. Therefore, it is crucial to further evaluate OS at different risk levels and identify new intervention targets. Many evidences suggest the important role of angiogenesis in OS, but further exploration is needed.

METHODS

We utilized public databases TARGET and GEO and employed bioinformatics algorithms such as LASSO, univariate and multivariate Cox regression analyses, and unsupervised consensus clustering to explore the role of angiogenesis-related genes (AGRGs) in OS. By calculating AGRG scores, we further analyzed OS molecular subtypes based on AGRGs. The correlation between AGRG scores and immune infiltration was subsequently examined. In vitro experiments, including WB, PCR, siRNA, migration, and invasion assays, were used to determine the value of the selected targets for OS.

RESULTS

Ultimately, we established an OS prognosis model based on five AGRGs (COL5A2, CXCL6, FSTL1, NRP1, and TNFRSF21) that can independently validate prognosis levels. In vitro experiments confirmed the aberrant expression of CXCL6 in OS and its potential role in migration and invasion.

CONCLUSION

Our study reveals the impact of angiogenesis on OS from a novel perspective and provides potential intervention targets.

摘要

背景

骨肉瘤(OS)作为最常见的原发性骨癌,其治疗效果仍不尽人意。因此,进一步评估不同风险水平的骨肉瘤并确定新的干预靶点至关重要。许多证据表明血管生成在骨肉瘤中起重要作用,但仍需进一步探索。

方法

我们利用公共数据库TARGET和GEO,并采用如LASSO、单变量和多变量Cox回归分析以及无监督一致性聚类等生物信息学算法,来探索血管生成相关基因(AGRGs)在骨肉瘤中的作用。通过计算AGRGs评分,我们进一步基于AGRGs分析骨肉瘤分子亚型。随后检测了AGRGs评分与免疫浸润之间的相关性。体外实验,包括蛋白质免疫印迹(WB)、聚合酶链反应(PCR)、小干扰RNA(siRNA)、迁移和侵袭实验,用于确定所选靶点对骨肉瘤的价值。

结果

最终,我们基于五个AGRGs(COL5A2、CXCL6、FSTL1、NRP1和TNFRSF21)建立了一个骨肉瘤预后模型,该模型能够独立验证预后水平。体外实验证实了CXCL6在骨肉瘤中的异常表达及其在迁移和侵袭中的潜在作用。

结论

我们的研究从一个新的角度揭示了血管生成对骨肉瘤的影响,并提供了潜在的干预靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec39/11377409/aae67d824367/12672_2024_1292_Fig1_HTML.jpg

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