Differential and Prognostic Significance of HOXB7 in Gliomas.

Xingang Zhou,Kun Yang,Zhiyuan Ma,Wenping Ma,Jiamin Chen,Tingyu Liang,Kenrick Ng,Chunxin Lv,Peng Wang,Jinhai Deng,Man Li

doi:10.3389/fcell.2021.697086

Abstract

Diffuse glioma is the most common primary tumor of the central nervous system. The prognosis of the individual tumor is heavily dependent on its grade and subtype. Homeobox B7 (HOXB7), a member of the homeobox family, is abnormally overexpressed in a variety of tumors. However, its function in glioma is unclear. In this study, HOXB7 mRNA and protein expression levels were analyzed in 401 gliomas from the CGGA RNA-seq database (325 cases) and our hospital (76 cases). HOXB7 expression, at both mRNA and protein levels, were upregulated in glioblastoma (GBM) and isocitrate dehydrogenase 1 (IDH1) wild-type glioma tissues. Kaplan–Meier with log-rank test showed that patients with high HOXB7 expression had a poor prognosis (p < 0.0001). Moreover, HOXB7 protein was deleted in 90.9% (20/22) of oligodendrogliomas and 13.0% (3/23) of astrocytomas. The sensitivity and specificity of HOXB7 protein deletion in oligodendroglioma were 90.9% (20/22) and 87.0% (20/23), respectively. To verify the reliability of using HOXB7 in differentiating oligodendroglioma, we used 1p/19q fluorescence in situ hybridization (FISH) testing as a positive control. The Cohen’s kappa coefficient of HOXB7 immunohistochemistry staining and 1p/19q FISH testing was 0.778 (95% CI: 0.594–0.962, p < 0.001). In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.

Highlights

Diffuse gliomas encompass a broad range of tumors affecting the central nervous system
We investigated the expression pattern of Homeobox B7 (HOXB7) in gliomas by analyzing the mRNA expression level of HOXB7 based on the RNA-seq data of 325 samples from the CGGA database
The results showed that the HOXB7 mRNA level was positively associated with World Health Organization (WHO) grade (R = 0.316, p < 0.001, Figure 2A) by Pearson’s correlation test

Summary

Introduction

Diffuse gliomas encompass a broad range of tumors affecting the central nervous system These include astrocytomas, oligodendrogliomas, and oligoastrocytomas, which range from Grade II to Grade IV according to the World Health Organization (WHO) classification system. Isocitrate dehydrogenase 1 (IDH1) mutation, which occurs early in gliomagenesis in WHO grade II and III gliomas, is an acknowledged molecular alteration (Binder et al, 2019). The demonstration of both IDH gene family mutation and combined whole-arm losses of 1p and 19q (1p/19q codeletion) is characteristic of oligodendrogliomas (Louis et al, 2016). There is an urgent need to identify specific markers for alternative diagnosis strategies for human glioma

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Results

Conclusion