Abstract:
So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM\'s relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann-Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic.
摘要:
到目前为止,胶质母细胞瘤(GBM)的细胞起源需要确定,流行的理论表明从转化的内源性干细胞中出现。成人神经发生主要发生在两个大脑区域:海马齿状回的脑室下区(SVZ)和颗粒下区(SGZ)。GBM与这些神经源性小生境的接近程度是否会影响患者的预后仍不确定。以前的研究通常依赖于主观评估,限制了这些结果的可靠性。在这项研究中,我们评估了GBM与皮质的关系的影响,SVZ和SGZ对临床变量使用全自动分割方法。在177例胶质母细胞瘤患者中,我们计算了到SVZ和SGZ的最小距离的最佳切点,以区分不良生存和有利生存。肿瘤与神经源性区接触对临床参数的影响,比如总体生存率,多焦点,MGMT启动子甲基化,Ki-67和KPS评分也通过多变量回归分析进行检查,卡方检验和Mann-Whitney-U.分析证实,与SVZ接触的肿瘤生存期较短,最佳切点为距SVZ14mm,将穷人与更有利的生存分开。相比之下,肿瘤与SGZ的接触对生存率没有负面影响.在接触SVZ的肿瘤中,我们没有发现与多灶性或MGMT启动子甲基化的显著相关性,正如以前的研究所讨论的那样。这些发现表明,需要对GBM和神经源性生态位之间的空间关系进行不同的评估。客观测量反驳了先前的假设,有必要对这一主题进行进一步的研究。