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胶质母细胞瘤的室下区接触与肿瘤数据的分子特征无关。

Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data.

机构信息

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

出版信息

Sci Rep. 2019 Feb 12;9(1):1842. doi: 10.1038/s41598-018-37734-w.

Abstract

Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ - GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ - GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases. An adjusted, multivariable analysis revealed that VSVZ contact was independently associated with decreased survival in both datasets. TCGA molecular data analyses revealed that VSVZ contact by GBM was independent of mutational, DNA methylation, gene expression, and protein expression signatures in the bulk tumor. Therefore, while survival of GBM patients is independently stratified by VSVZ contact, with VSVZ + GBM patients displaying a poor prognosis, the VSVZ + GBMs do not possess a distinct molecular signature at the bulk sample level. Focused examination of the interplay between the VSVZ microenvironment and subsets of GBM cells proximal to this region is warranted.

摘要

胶质母细胞瘤(GBM)与脑室下区(VSVZ)干细胞巢接触的患者,其生存情况是否与 VSVZ-GBM 患者不同,且与其他已知的预测因子或分子特征无关,目前尚不清楚。本研究采用多变量 Cox 分析来调整生存的广泛接受的预测因子,在 170 例单机构患者和包含在癌症基因组图谱(TCGA)和成像图谱(TCIA)中的 254 例患者中,计算了 VSVZ+GBM 和 VSVZ-GBM 患者的总生存(OS)和无进展生存(PFS)的危险比(HR)。调整后的多变量分析表明,VSVZ 接触与两个数据集的生存降低独立相关。TCGA 分子数据分析表明,GBM 与 VSVZ 的接触与肿瘤内的突变、DNA 甲基化、基因表达和蛋白表达特征无关。因此,虽然 VSVZ 接触可独立分层 GBM 患者的生存情况,但 VSVZ+GBM 患者预后较差,但 VSVZ+GBM 在大量样本水平上并不具有独特的分子特征。值得关注的是,VSVZ 微环境与该区域附近的 GBM 细胞亚群之间的相互作用。

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