Microglia-Specific Expression of HEXA and HEXB Leads to Poor Prognosis in Glioblastoma Patients

Mengxian Jia,Jiashu Lian,Wenbin Zhang,Zhihui Huang,Ying Wang,Changgang Huang,Honglin Teng,Junle Zhu,Jian Zhou

doi:10.3389/fonc.2021.685893

Abstract

Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. β-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, HEXA and HEXB, are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD). However, the expression pattern and function of HEXA and HEXB in GBM remains unclear. Here, we found that both the mRNA and protein expression levels of HEXA and HEXB were significantly upregulated in GBM patient samples. The results from single-cell RNA-sequencing (scRNA-seq) database and double immunostaining showed that HEXA and HEXB were specifically expressed in microglia in GBM patient samples. Furthermore, our in vitro experiments revealed that conditioned media from HEXA and HEXB knockdown-microglia cells could inhibit the proliferation and migration of GBM cells. Finally, according to survival analysis based on online database, higher expression of HEXA and HEXB was associated with poor prognosis in GBM patients. In conclusion, these results suggest that microglial HEXA and HEXB play fundamental role in GBM progression, and they will be potential biomarkers for GBM.

Highlights

Glioblastoma, known as glioblastoma multiforme (GBM), is the most prevalent malignant tumor of human brain [1]
No apparent statistical differences in mRNA levels of HEXA and HEXB between the primary, recurrent, and secondary groups were observed (Figures 1E, F). These results suggest that mRNA levels of HEXA and HEXB are upregulated in GBM and that their expression level is positively correlated with the grade of glioma
We found that HEXA and HEXB were highly expressed in the microglia of GBM tissues and could promote the progression of GBM by secreting some factors

Summary

Introduction

Glioblastoma, known as glioblastoma multiforme (GBM), is the most prevalent malignant tumor of human brain [1]. The annual incidence of GBM is 3.19 per 100, 000 individuals, the highly invasive and heterogeneous features of GBM as grade IV glioma leads to its poor prognosis [2, 3]. The available treatment options for this tumor are currently limited. The standard treatment for GBM patients is surgical resection, followed by radiotherapy and administration of temozolomide [4]. These treatments do not lead to desirable outcomes. With the development of sequencing technologies and bioinformatics analysis, an increasing number of biomarkers have been found for the diagnosis of GBM, which can lead to its timely detection and

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Conclusion