在IDH1状态不同的胶质瘤患者中,ZEB1和YAP1的过表达与预后不良有关。

IF 1.1 Q4 ONCOLOGY International journal of clinical and experimental pathology Pub Date : 2023-07-15 eCollection Date: 2023-01-01
Na Miao, Zhi-Qiang Wang, Ning Zhang, Zhi-Ping Ma, Li-Ping Su, Yang-Yang Zhai, Yan-Ran Hu, Wei Sang, Wei Zhang
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引用次数: 0

摘要

目的:锌指E盒结合同源物1(ZEB1)和Yes相关蛋白1(YAP1)与胶质瘤的临床预后是否存在相关性仍不清楚。因此,本研究旨在探讨ZEB1和YAP1对人类胶质瘤预后的影响及其与异柠檬酸脱氢酶1(IDH1)基因状态的关系:免疫组化染色法记录了122例低级别胶质瘤(LGGs)和69例胶质母细胞瘤(GBMs)中ZEB1、YAP1和p-YAP1的表达水平。ZEB1和YAP1与病理数据的相关性采用皮尔逊卡方检验。然后采用斯皮尔曼相关分析法分析 YAP1、ZEB1 和 IDH1 基因状态之间的关系。通过生存分析研究了ZEB1和YAP1对预后的影响:我们在 29 例 LGG(23.8%)和 39 例 GBM(56.5%)中检测到 ZEB1 的高表达水平,在 22 例 LGG(18.0%)和 44 例 GBM(63.8%)中检测到 YAP1 的高表达水平。这些结果表明,ZEB1 和 YAP1 在 GBM 中的蛋白表达水平更高(P < 0.001)。ZEB1 和 YAP1 之间存在明显的正相关(P < 0.001; r = 0.533)。ZEB1的高表达与肿瘤分级(P < 0.001)和Ki-67(P = 0.0037)有关。YAP1过表达与Ki-67(P < 0.001)、P53(P = 0.009)、肿瘤分级(P < 0.001)和肿瘤位置(P = 0.018)相关。ZEB1和YAP1高表达的患者总生存期(OS)较差(P < 0.001)。多变量分析显示,YAP1是影响OS的独立预后因素。在LGG组中,观察到YAP1表达水平升高的胶质瘤患者的OS更差。斯皮尔曼相关性分析显示,ZEB1表达与IDH1状态无相关性(P = 0.360; r = -0.084),而YAP1表达与IDH1突变呈负相关(P < 0.001, r = -0.364):我们的研究表明,ZEB1和YAP1在GBM中被显著激活,ZEB1和YAP1高表达的患者OS较差。在胶质瘤中,ZEB1的表达与YAP1明显相关。ZEB1和YAP1的共表达可作为胶质瘤有用的预后生物标志物,YAP1的异常表达可能与IDH1基因状态有关。
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Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

Objective: Whether there is a correlation between zinc-finger E-box-binding homolog 1 (ZEB1) and Yes-associated protein 1 (YAP1) with clinical outcome in gliomas remains unclear. Hence, this study aimed to investigate the effects of ZEB1 and YAP1 on the prognosis of human gliomas and its relationship with the isocitrate dehydrogenase 1 (IDH1) gene state.

Methods: Immunohistochemical staining was used to record the expression levels of ZEB1, YAP1, and p-YAP1 in 122 cases of low-grade glioma (LGGs) and 69 cases of glioblastoma (GBMs). The correlations of ZEB1 and YAP1 with pathological data were determined by Pearson's Chi-square test. Spearman correlation analysis was then used for analyzing the relationship among YAP1, ZEB1, and IDH1 gene status. The effects of ZEB1 and YAP1 on prognosis were investigated through survival analysis.

Results: We detected high ZEB1 expression levels in 29 LGGs (23.8%) and 39 GBMs (56.5%), and high YAP1 expression levels in 22 LGGs (18.0%) and 44 of GBM (63.8%). These results revealed that the protein expression levels of ZEB1 and YAP1 were higher in GBM (P < 0.001). There was a significantly positive correlation between ZEB1 and YAP1 (P < 0.001; r = 0.533). High ZEB1 expression was related to tumor grade (P < 0.001) and Ki-67 (P = 0.0037). YAP1 overexpression was correlated with Ki-67 (P < 0.001), P53 (P = 0.009), tumor grade (P < 0.001), and tumor location (P = 0.018). Patients with ZEB1 and YAP1 high expression had worse overall survival (OS) (P < 0.001). The multivariate analysis showed that YAP1 was an independent prognostic factor for OS. In the LGG group, worse OS were observed in glioma patients with elevated YAP1 expression level. Spearman correlation analysis revealed no association between ZEB1 expression and IDH1 state (P = 0.360; r = -0.084), and YAP1 expression had a negative correlation with IDH1 mutation (P < 0.001, r = -0.364).

Conclusions: Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.

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期刊介绍: The International Journal of Clinical and Experimental Pathology (IJCEP, ISSN 1936-2625) is a peer reviewed, open access online journal. It was founded in 2008 by an international group of academic pathologists and scientists who are devoted to the scientific exploration of human disease and the rapid dissemination of original data. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal.
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