跨平台分析揭示胶质母细胞瘤侵袭的细胞和分子景观。
Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion.
机构信息
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Department of Neurosurgery, Yale University, New Haven, CT, USA.
出版信息
Neuro Oncol. 2023 Mar 14;25(3):482-494. doi: 10.1093/neuonc/noac186.
BACKGROUND
Improved treatment of glioblastoma (GBM) needs to address tumor invasion, a hallmark of the disease that remains poorly understood. In this study, we profiled GBM invasion through integrative analysis of histological and single-cell RNA sequencing (scRNA-seq) data from 10 patients.
METHODS
Human histology samples, patient-derived xenograft mouse histology samples, and scRNA-seq data were collected from 10 GBM patients. Tumor invasion was characterized and quantified at the phenotypic level using hematoxylin and eosin and Ki-67 histology stains. Crystallin alpha B (CRYAB) and CD44 were identified as regulators of tumor invasion from scRNA-seq transcriptomic data and validated in vitro, in vivo, and in a mouse GBM resection model.
RESULTS
At the cellular level, we found that invasive GBM are less dense and proliferative than their non-invasive counterparts. At the molecular level, we identified unique transcriptomic features that significantly contribute to GBM invasion. Specifically, we found that CRYAB significantly contributes to postoperative recurrence and is highly co-expressed with CD44 in invasive GBM samples.
CONCLUSIONS
Collectively, our analysis identifies differentially expressed features between invasive and nodular GBM, and describes a novel relationship between CRYAB and CD44 that contributes to tumor invasiveness, establishing a cellular and molecular landscape of GBM invasion.
背景
提高胶质母细胞瘤（GBM）的治疗效果需要解决肿瘤侵袭问题，这是该疾病的一个标志，但目前仍了解甚少。在这项研究中，我们通过对 10 名患者的组织学和单细胞 RNA 测序（scRNA-seq）数据进行综合分析，对 GBM 的侵袭进行了分析。
方法
从 10 名 GBM 患者中收集了人类组织学样本、患者来源的异种移植小鼠组织学样本和 scRNA-seq 数据。使用苏木精和伊红（H&E）和 Ki-67 组织学染色在表型水平上对肿瘤侵袭进行了特征描述和量化。从 scRNA-seq 转录组数据中鉴定出晶体蛋白 alpha B (CRYAB)和 CD44 是肿瘤侵袭的调节剂，并在体外、体内和小鼠 GBM 切除模型中进行了验证。
结果
在细胞水平上，我们发现侵袭性 GBM 比非侵袭性 GBM 密度更低，增殖能力更差。在分子水平上，我们发现了一些独特的转录组特征，这些特征对 GBM 的侵袭有显著贡献。具体来说，我们发现 CRYAB 显著促进了术后复发，并且在侵袭性 GBM 样本中与 CD44 高度共表达。
结论
总的来说，我们的分析确定了侵袭性和结节性 GBM 之间差异表达的特征，并描述了 CRYAB 和 CD44 之间的新关系，这有助于肿瘤的侵袭性，建立了 GBM 侵袭的细胞和分子图谱。
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