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成人脊髓髓内星形细胞瘤的转录组图谱及分子通路激活特征

Transcriptomic Portraits and Molecular Pathway Activation Features of Adult Spinal Intramedullary Astrocytomas.

作者信息

Konovalov Nikolay, Timonin Stanislav, Asyutin Dmitry, Raevskiy Mikhail, Sorokin Maxim, Buzdin Anton, Kaprovoy Stanislav

机构信息

Burdenko Neurosurgical Center, Moscow, Russia.

Omicsway Corp., Walnut, CA, United States.

出版信息

Front Oncol. 2022 Mar 21;12:837570. doi: 10.3389/fonc.2022.837570. eCollection 2022.

Abstract

In this study, we report 31 spinal intramedullary astrocytoma (SIA) RNA sequencing (RNA-seq) profiles for 25 adult patients with documented clinical annotations. To our knowledge, this is the first clinically annotated RNA-seq dataset of spinal astrocytomas derived from the intradural intramedullary compartment. We compared these tumor profiles with the previous healthy central nervous system (CNS) RNA-seq data for spinal cord and brain and identified SIA-specific gene sets and molecular pathways. Our findings suggest a trend for SIA-upregulated pathways governing interactions with the immune cells and downregulated pathways for the neuronal functioning in the context of normal CNS activity. In two patient tumor biosamples, we identified diagnostic fusion oncogenes, and we also found 16 new SIA-associated fusion transcripts. In addition, we bioinformatically simulated activities of targeted cancer drugs in SIA samples and predicted that several tyrosine kinase inhibitory drugs and thalidomide analogs could be potentially effective as second-line treatment agents to aid in the prevention of SIA recurrence and progression.

摘要

在本研究中,我们报告了25例有临床记录注释的成年患者的31份脊髓髓内星形细胞瘤(SIA)RNA测序(RNA-seq)图谱。据我们所知,这是首个来自硬脊膜内髓内区域的脊髓星形细胞瘤的有临床注释的RNA-seq数据集。我们将这些肿瘤图谱与先前脊髓和脑的健康中枢神经系统(CNS)RNA-seq数据进行比较,确定了SIA特异性基因集和分子通路。我们的研究结果表明,在正常CNS活动的背景下,SIA上调的通路调控与免疫细胞的相互作用,而下调的通路则与神经元功能有关。在两份患者肿瘤生物样本中,我们鉴定出诊断性融合癌基因,还发现了16种新的SIA相关融合转录本。此外,我们通过生物信息学模拟了靶向抗癌药物在SIA样本中的活性,并预测几种酪氨酸激酶抑制药物和沙利度胺类似物可能作为二线治疗药物有效,有助于预防SIA复发和进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded6/8978956/853a45bf5a35/fonc-12-837570-g001.jpg

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