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CTSL 在 GBM 上作为 COVID-19 靶点的表达和意义。

Expressions and significances of CTSL, the target of COVID-19 on GBM.

机构信息

Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, People's Republic of China.

Key Laboratory of Neurology of Gansu Province, Lanzhou, 730030, Gansu, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2022 Mar;148(3):599-608. doi: 10.1007/s00432-021-03843-9. Epub 2021 Nov 22.

Abstract

INTRODUCTION

Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection. We investigated the association between the expression level of CTSL and overall survival in Glioblastoma multiforme (GBM) patients, to better understand the possible route and risks of new coronavirus infection for patients with GBM.

METHODS

The expression level of CTSL in GBM was analyzed using TCGA and CGGA databases. The relationship between CTSL and immune infiltration levels was analyzed by means of the TIMER database. The impact of CTSL inhibitors on GBM biological activity was tested.

RESULTS

The findings revealed that GBM tissues had higher CTSL expression levels than that of normal brain tissues, which was associated with a significantly lower survival rate in GBM patients. Meanwhile, the expression level of CTSL negatively correlated with purity, B cell and CD8 T cell in GBM. CTSL inhibitor significantly reduced growth and induced mitochondrial apoptosis.

CONCLUSION

According to the findings, CTSL acts as an independent prognostic factor and can be considered as promising therapeutic target for GBM.

摘要

简介

组织蛋白酶 L(CTSL)是一种与 SARS 进入相关的 SARS-CoV-2 蛋白酶,在病毒进入细胞及随后的感染中起关键作用。我们研究了 CTSL 的表达水平与胶质母细胞瘤(GBM)患者总生存率之间的关系,以更好地了解新的冠状病毒感染患者的可能途径和风险。

方法

使用 TCGA 和 CGGA 数据库分析 GBM 中 CTSL 的表达水平。通过 TIMER 数据库分析 CTSL 与免疫浸润水平的关系。测试 CTSL 抑制剂对 GBM 生物学活性的影响。

结果

研究结果表明,GBM 组织中的 CTSL 表达水平高于正常脑组织,与 GBM 患者的生存率显著降低相关。同时,CTSL 的表达水平与 GBM 的纯度、B 细胞和 CD8 T 细胞呈负相关。CTSL 抑制剂显著抑制了肿瘤的生长并诱导了线粒体凋亡。

结论

根据这些发现,CTSL 作为一个独立的预后因素,可以被认为是 GBM 有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27ef/11800775/5ca7835b9423/432_2021_3843_Fig1_HTML.jpg

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