Research Paper|Volume 12, Issue 24|pp 24995—25004

DZIP3 is a key factor to stratify IDH1 wild-type lower-grade gliomas

Tingyu Liang¹, Xingang Zhou², Peiliang Li¹, Gan You³, Fang Wang¹, Peng Wang², Enshan Feng¹

¹Department of Neurosurgery, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
²Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
³Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China

* Equal contribution

Received: August 23, 2019Accepted: July 16, 2020Published: November 21, 2020

Copyright: © 2020 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Malignant glioma is the most common form of primary malignant brain cancer. Heterogeneity is the hallmark of glioma. DAZ-interacting zinc finger 3 (DZIP3), acts as an RNA-binding RING-type ubiquitin ligase; however, its function in glioma is yet unclear.

Results: The DZIP3 expression was related to the World Health Organization (WHO) grade and isocitrate dehydrogenase 1(IDH1) status, as well as the clinical outcome. Malignant cases exhibit lower DZIP3 expression. DZIP3 was an independent predictive factor of good prognosis in all grade and lower grade gliomas (p < 0.0001). Gene enrichment analysis and immunohistochemistry indicated that DZIP3 affected the biological behavior of glioma through the angiogenesis pathway. Moreover, based on DZIP3 expression, IDH1 wild-type lower-grade gliomas could be divided into two groups with different survival time.

Conclusion: In conclusion, the loss of DZIP3 may be involved in the mechanism of angiogenesis in the invasive biological process of glioma. These findings laid an understanding of DZIP3-specific clinical features in glioma.

Methods: A total of 325 glioma patients from the Chinese Glioma Genome Atlas (CGGA) RNA-seq cohort comprised the training cohort, while 265 patients from the GSE 16011 array cohort formed the validation cohort. The mRNA expression of DZIP3 and clinical characteristics was assessed. DZIP3 protein expression and microvessel density (MVD) were evaluated by immunohistochemistry (IHC).