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NDRG1表达在高级别胶质瘤血管生成拟态中的作用

The Role of NDRG1 Expression in Vasculogenic Mimicry of High-grade Gliomas.

作者信息

Yang Haoxiaoyu, Qin Xuqiu, Zhang Ruihao, Miao Jiayi, Cui Jiangli, Li Yi, Miao Xingyu

机构信息

Department of Neurosurgery, Shaanxi Provincial People's Hospital, Xi'an, China.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

J Cancer. 2024 Oct 28;15(20):6631-6643. doi: 10.7150/jca.100458. eCollection 2024.

Abstract

Glioma is one of the most common primary malignant tumors of the central nervous system, and the prognosis is getting worse with the improvement of tumor grade. In recent years, with the in-depth study of the disease, researchers have found that microvascular mimicry seems to be the key factor of poor prognosis, but its specific mechanism has not been thoroughly studied, and the expression of microvascular mimicry in high-grade gliomas is closely related to the expression of NDRG1 gene. This research project is expected to control the occurrence and development of HGG by exploring the factors that affect the expression of NDRG1 gene. Retrospective RNA-seq data analysis was performed on Chinese Glioma Genome Atlas (CGGA) database and glioma patients from TCGA. Subsequently, 7 cases of CNSWHO3 grade patients and 36 cases of CNSWHO4 grade patients were selected based on postoperative pathological results, and clinical information of the patients was collected. Immunohistochemical staining of relevant proteins was conducted on patient tissues, and the results were recorded after double immunostaining scoring for each slide. Statistical analysis of the data was performed using relevant statistical methods. The analysis of two databases shows that NDRG1 is enriched in HGG samples. NDRG1 is an independent risk factor for overall survival (OS) in glioma patients, and plays an important role in promoting VM in glioma patients. Different protein immunohistochemistry double immunostaining scores show that the expression levels of NDRG1 and Vimentin are correlated with tumor grade in HGG patients. The expression of VM in samples is closely related to the expression level of NDRG1 (P=3.98E-04) and tumor CNSWHO grade (P=0.019). MVD in HGG patients is related to NDRG1 expression (P=0.035). The rest of the immunohistochemistry scores are not statistically significant (P>0.05). There is a trend of correlation between Vimentin expression and MVD in CNSWHO grade 4 HGG patients (P=0.07). NDRG1 exerts adverse effects on the CNSWHO grading of HGG by regulating the expression of VM and MVD in HGG patients, as well as the tumor EMT process.

摘要

胶质瘤是中枢神经系统最常见的原发性恶性肿瘤之一,并且随着肿瘤分级的升高预后越来越差。近年来,随着对该疾病研究的深入,研究人员发现微血管拟态似乎是预后不良的关键因素,但其具体机制尚未得到深入研究,且高级别胶质瘤中微血管拟态的表达与NDRG1基因的表达密切相关。本研究项目有望通过探索影响NDRG1基因表达的因素来控制高级别胶质瘤的发生发展。对中国胶质瘤基因组图谱(CGGA)数据库和来自TCGA的胶质瘤患者进行了回顾性RNA测序数据分析。随后,根据术后病理结果选取了7例中枢神经系统WHO3级患者和36例中枢神经系统WHO4级患者,并收集了患者的临床信息。对患者组织进行相关蛋白的免疫组织化学染色,并在对每张玻片进行双重免疫染色评分后记录结果。使用相关统计方法对数据进行统计分析。两个数据库的分析表明,NDRG1在高级别胶质瘤样本中富集。NDRG1是胶质瘤患者总生存期(OS)的独立危险因素,并且在促进胶质瘤患者的微血管拟态中起重要作用。不同的蛋白免疫组织化学双重免疫染色评分表明,高级别胶质瘤患者中NDRG1和波形蛋白的表达水平与肿瘤分级相关。样本中微血管拟态的表达与NDRG1的表达水平(P = 3.98E - 04)和肿瘤中枢神经系统WHO分级(P = 0.019)密切相关。高级别胶质瘤患者的微血管密度(MVD)与NDRG1表达相关(P = 0.035)。其余免疫组织化学评分无统计学意义(P>0.05)。在中枢神经系统WHO4级高级别胶质瘤患者中,波形蛋白表达与微血管密度之间存在相关趋势(P = 0.07)。NDRG1通过调节高级别胶质瘤患者中微血管拟态和微血管密度的表达以及肿瘤上皮 - 间质转化(EMT)过程,对高级别胶质瘤的中枢神经系统WHO分级产生不利影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fb3/11632992/b2a3ee9e0be2/jcav15p6631g001.jpg

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