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基于细胞外囊泡的癌症检测板对胶质母细胞瘤具有高灵敏度和特异性诊断能力。

Extracellular-Vesicle-Based Cancer Panels Diagnose Glioblastomas with High Sensitivity and Specificity.

作者信息

Mut Melike, Adiguzel Zelal, Cakir-Aktas Canan, Hanalioğlu Şahin, Gungor-Topcu Gamze, Kiyga Ezgi, Isikay Ilkay, Sarac Aydan, Soylemezoglu Figen, Strobel Thomas, Ampudia-Mesias Elisabet, Cameron Charles, Aslan Tulay, Tekirdas Eray, Hayran Mutlu, Oguz Kader Karli, Henzler Christine, Saydam Nurten, Saydam Okay

机构信息

Department of Neurosurgery, Faculty of Medicine, Hacettepe University, Ankara 06230, Turkey.

Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06230, Turkey.

出版信息

Cancers (Basel). 2023 Jul 26;15(15):3782. doi: 10.3390/cancers15153782.

Abstract

Glioblastoma is one of the most devastating neoplasms of the central nervous system. This study focused on the development of serum extracellular vesicle (EV)-based glioblastoma tumor marker panels that can be used in a clinic to diagnose glioblastomas and to monitor tumor burden, progression, and regression in response to treatment. RNA sequencing studies were performed using RNA isolated from serum EVs from both patients ( = 85) and control donors ( = 31). RNA sequencing results for preoperative glioblastoma EVs compared to control EVs revealed 569 differentially expressed genes (DEGs, 2XFC, FDR < 0.05). By using these DEGs, we developed serum-EV-based biomarker panels for the following glioblastomas: wild-type IDH1 (96% sensitivity/80% specificity), MGMT promoter methylation (91% sensitivity/73% specificity), p53 gene mutation (100% sensitivity/89% specificity), and TERT promoter mutation (89% sensitivity/100% specificity). This is the first study showing that serum-EV-based biomarker panels can be used to diagnose glioblastomas with a high sensitivity and specificity.

摘要

胶质母细胞瘤是中枢神经系统最具破坏性的肿瘤之一。本研究聚焦于基于血清细胞外囊泡(EV)的胶质母细胞瘤肿瘤标志物组的开发,这些标志物组可用于临床诊断胶质母细胞瘤,并监测肿瘤负荷、进展以及对治疗的反应(包括消退情况)。使用从患者(n = 85)和对照供体(n = 31)的血清EV中分离出的RNA进行RNA测序研究。术前胶质母细胞瘤EV与对照EV的RNA测序结果显示有569个差异表达基因(DEG,2倍变化倍数,FDR < 0.05)。通过使用这些DEG,我们开发了基于血清EV的生物标志物组,用于诊断以下胶质母细胞瘤:野生型IDH1(敏感性96%/特异性80%)、MGMT启动子甲基化(敏感性91%/特异性73%)、p53基因突变(敏感性100%/特异性89%)和TERT启动子突变(敏感性89%/特异性100%)。这是第一项表明基于血清EV的生物标志物组可用于高敏感性和特异性诊断胶质母细胞瘤的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/375a/10417317/4454e62cd3ff/cancers-15-03782-g001.jpg

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