荷兰伊拉斯谟医学中心神经内科Pim J. French研究团队利用转录组分析揭示胶质母细胞瘤的肿瘤微环境变化。相关论文发表在2023年3月9日出版的《癌细胞》杂志上。

他们对接受当前护理标准治疗的患者的配对原发性 - 复发性胶质母细胞瘤切除术进行RNA测序（RNA-seq）（n = 322测试，n = 245验证）。转录亚型在二维空间中形成相互连接的连续体。复发性肿瘤显示优先间充质进展。随着时间的推移，标志性的胶质母细胞瘤基因不会发生显著改变。相反，肿瘤纯度随着时间的推移而降低，并伴随着神经元和少突胶质细胞标志基因以及独立肿瘤相关巨噬细胞的共同增加。

这些组成变化通过单细胞RNA-seq和免疫组织化学证实。细胞外基质相关基因集在复发和体积增加时增加，单细胞RNA和免疫组织化学表明它主要由周细胞表达。这种特征与复发时生存率显著降低有关。他们的数据表明，胶质母细胞瘤主要通过微环境（重新）组织而不是肿瘤细胞的分子进化。

据介绍，更好地了解IDH野生型胶质母细胞瘤的转录进化对于治疗优化至关重要。

附：英文原文

Title: Transcriptome analysis reveals tumor microenvironment changes in glioblastoma

Author: Youri Hoogstrate, Kaspar Draaisma, Santoesha A. Ghisai, Levi van Hijfte, Nastaran Barin, Iris de Heer, Wouter Coppieters, Thierry P.P. van den Bosch, Anne Bolleboom, Zhenyu Gao, Arnaud J.P.E. Vincent, Latifa Karim, Manon Deckers, Martin J.B. Taphoorn, Melissa Kerkhof, Astrid Weyerbrock, Marc Sanson, Ann Hoeben, Slávka Lukacova, Giuseppe Lombardi, Sieger Leenstra, Monique Hanse, Ruth E.M. Fleischeuer, Colin Watts, Nicos Angelopoulos, Thierry Gorlia, Vassilis Golfinopoulos, Vincent Bours, Martin J. van den Bent, Pierre A. Robe, Pim J. French

Issue&Volume: 2023-03-09

Abstract: A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells.

DOI: 10.1016/j.ccell.2023.02.019

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00047-8