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多组学分析揭示了骨形态发生蛋白在多种癌症中的全景图。

Multi-Omics Analysis Reveals the Pan-Cancer Landscape of Bone Morphogenetic Proteins.

机构信息

Department of Orthopedics, Ningbo Hangzhou Bay Hospital, Ningbo, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2020 Apr 5;26:e920943. doi: 10.12659/MSM.920943.

Abstract

BACKGROUND Bone morphogenetic proteins (BMPs) are widely involved in cancer development. However, a wealth of conflicting data raises the question of whether BMPs serve as oncogenes or as cancer suppressors. MATERIAL AND METHODS By integrating multi-omics data across cancers, we comprehensively analyzed the genomic and pharmacogenomic landscape of BMP genes across cancers. RESULTS Surprisingly, our data indicate that BMPs are globally downregulated in cancers. Further genetics and epigenetics analyses show that this abnormal expression is driven by copy number variations, especially heterozygous amplification. We next assessed the BMP-associated pathways and demonstrated that they suppress cell cycle and estrogen hormone pathways. Bone morphogenetic protein interacts with 58 compounds, and their dysfunction can induce drug sensitivity. CONCLUSIONS Our results define the landscape of the BMP family at a systems level and open potential therapeutic opportunities for cancer patients.

摘要

背景

骨形态发生蛋白(BMPs)广泛参与癌症的发生发展。然而,大量相互矛盾的数据引发了这样的疑问:BMPs 是癌基因还是抑癌基因?

方法

通过整合癌症的多组学数据,我们全面分析了癌症中 BMP 基因的基因组和药物基因组学特征。

结果

令人惊讶的是,我们的数据表明 BMPs 在癌症中整体下调。进一步的遗传学和表观遗传学分析表明,这种异常表达是由拷贝数变异驱动的,尤其是杂合扩增。接下来,我们评估了与 BMP 相关的通路,并证实它们抑制了细胞周期和雌激素通路。骨形态发生蛋白与 58 种化合物相互作用,其功能障碍可导致药物敏感性。

结论

我们的研究结果从系统水平上定义了 BMP 家族的图谱,并为癌症患者带来了潜在的治疗机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6070/7156877/18c330fa5fce/medscimonit-26-e920943-g001.jpg

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