Effects of BMPER, CXCL10, and HOXA9 on Neovascularization During Early-Growth Stage of Primary High-Grade Glioma and Their Corresponding MRI Biomarkers

Wei Xue; Junfeng Zhang; Haipeng Tong; Tian Xie; Xiao Chen; Bo Zhou; Pengfei Wu; Peng Zhong; Xuesong Du; Yu Guo; Youyuan Yang; Heng Liu; Jingqin Fang; Shunan Wang; Hao Wu; Kai Xu; Weiguo Zhang

doi:10.3389/fonc.2020.00711

Effects of BMPER, CXCL10, and HOXA9 on Neovascularization During Early-Growth Stage of Primary High-Grade Glioma and Their Corresponding MRI Biomarkers

Front Oncol. 2020 May 5:10:711. doi: 10.3389/fonc.2020.00711. eCollection 2020.

Authors

Wei Xue¹, Junfeng Zhang¹, Haipeng Tong¹, Tian Xie¹, Xiao Chen¹, Bo Zhou¹, Pengfei Wu², Peng Zhong³, Xuesong Du¹, Yu Guo¹, Youyuan Yang¹, Heng Liu^{1

4}, Jingqin Fang¹, Shunan Wang¹, Hao Wu¹, Kai Xu¹, Weiguo Zhang^{1

5}

Affiliations

¹ Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.
² Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing, China.
³ Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China.
⁴ Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing, China.
⁵ Chongqing Clinical Research Centre of Imaging and Nuclear Medicine, Chongqing, China.

Abstract

Neovascularization is required in high-grade glioma (HGG). The objective of this study was to explore neovascularization-related genes and their corresponding MRI biomarkers during the early-growth stage of HGG. Tumor tissues from 30 HGG patients underwent perfusion MRI scanning prior to surgery were used to establish orthotopic xenograft models, pathologically analyze the tumor vasculature and perform transcriptome sequencing. The cases were divided into two groups based on whether the xenograft was successfully established. Microvascular density and BMPER, CXCL10, and HOXA9 expression of surgical specimens in the xenograft-forming group was significantly elevated and the microvascular diameter was significantly reduced, in vitro inhibition of BMPER, CXCL10, or HOXA9 in the glioma stem cell significantly suppressed its tube formation abilities. The in vivo experiment showed that BMPER was highly expressed in the early tumor growth phase (20 days), CXCL10 and HOXA9 expression was elevated with tumor progress, and spatially associated with tumor vasculature. Perfusion weighted MRI (PWI-MRI) derived parameters, rCBV, rCBF, K_trans, and V_p, were also increased in the xenograft-forming group. In conclusion BMPER, CXCL10, and HOXA9 promote early tumor growth and progression by stimulating neovascularization of primary HGG. The rCBV, rCBF, K_trans, and V_p can be used as imaging biomarkers to predict the expression statuses of these genes.

Keywords: BMPER; CXCL10; HOXA9; PWI-MRI; high-grade glioma; neovascularization.