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全血液体活检用于鉴定与胶质母细胞瘤WHO CNS 4级复发相关的基因表达模式(mRNA和miRNA)

Liquid Biopsy in Whole Blood for Identification of Gene Expression Patterns (mRNA and miRNA) Associated with Recurrence of Glioblastoma WHO CNS Grade 4.

作者信息

Muhtadi Razan, Bernhardt Denise, Multhoff Gabriele, Hönikl Lisa, Combs Stephanie E, Krieg Sandro M, Gempt Jens, Meyer Bernhard, Barsegian Vahé, Lindemann Monika, Kasper Mandy, Stewart Samantha, Port Matthias, Abend Michael, Diehl Christian D, Ostheim Patrick

机构信息

Bundeswehr Institute of Radiobiology, 80937 Munich, Germany.

Graduate Center of Medicine and Health, Technical University Munich, 81675 Munich, Germany.

出版信息

Cancers (Basel). 2024 Jun 26;16(13):2345. doi: 10.3390/cancers16132345.

DOI:10.3390/cancers16132345
PMID:39001407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11240769/
Abstract

GBM WHO CNS Grade 4 represents a major challenge for oncology due to its aggressive behavior. Conventional imaging has restrictions in detecting tumor recurrence. This prospective study aims to identify gene-based biomarkers in whole blood instead of isolating exosomes for the early detection of tumor recurrence. Blood samples (n = 33) were collected from seven GBM patients at time points before and after surgery as well as upon tumor recurrence. Four tumor tissue samples were assessed in parallel. Next-generation sequencing (NGS), including mRNA-seq and small RNA-seq, was used to analyze gene expression profiles in blood samples and tumor tissues. A novel filtering pipeline was invented to narrow down potential candidate genes. In total, between 6-93 mRNA and 1-19 small RNA candidates could be identified among the seven patients. The overlap of genes between the patients was minimal, indicating significant inter-individual variance among GBM patients. In summary, this prospective study supports the applicability of gene expression measurements in whole blood for the detection of tumor recurrence. It might provide an alternative to the challenging workflow of liquid biopsy after laborious exosome isolation from whole blood.

摘要

世界卫生组织中枢神经系统4级胶质母细胞瘤(GBM)因其侵袭性而成为肿瘤学面临的一项重大挑战。传统成像在检测肿瘤复发方面存在局限性。这项前瞻性研究旨在识别全血中基于基因的生物标志物,而非分离外泌体用于肿瘤复发的早期检测。在手术前后以及肿瘤复发时,从7名GBM患者采集了血样(n = 33)。同时评估了4份肿瘤组织样本。采用包括mRNA测序和小RNA测序在内的新一代测序(NGS)技术分析血样和肿瘤组织中的基因表达谱。发明了一种新型筛选流程以缩小潜在候选基因范围。在这7名患者中,总共可识别出6至93个mRNA候选基因和1至19个小RNA候选基因。患者之间的基因重叠极少,表明GBM患者之间存在显著的个体差异。总之,这项前瞻性研究支持全血基因表达检测用于肿瘤复发检测的适用性。它可能为从全血中费力分离外泌体后进行的具有挑战性的液体活检工作流程提供一种替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/ccab5e09f847/cancers-16-02345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/4ca88d735165/cancers-16-02345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/a9b1eaf410e1/cancers-16-02345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/84f04e342c25/cancers-16-02345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/ccab5e09f847/cancers-16-02345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/4ca88d735165/cancers-16-02345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/a9b1eaf410e1/cancers-16-02345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/84f04e342c25/cancers-16-02345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff80/11240769/ccab5e09f847/cancers-16-02345-g004.jpg

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本文引用的文献

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Cancers (Basel). 2023 Jul 26;15(15):3790. doi: 10.3390/cancers15153790.
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Liquid biopsy and glioblastoma.液体活检与胶质母细胞瘤
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Comparing Two Methods for the Isolation of Exosomes.比较两种外泌体分离方法。
软组织肉瘤患者报告结局测量 25 年的经验:系统评价。
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T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10.在神经胶质瘤微环境中,髓系细胞释放白细胞介素 10 介导 T 细胞功能障碍。
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