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

Background: 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. Methods: 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. Results: 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). Conclusions: 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.