Stemness and clinical features in relation to the subventricular zone in diffuse lower-grade glioma: an exploratory study

Abstract

Background The subventricular zone (SVZ) of the human brain is a site of adult stem cell proliferation and a microenvironment for neural stem cells (NSCs). It has been suggested that NSCs in the SVZ are potential cells of origin containing driver mutations of glioblastoma, but their role in the origin of diffuse lower-grade gliomas (dLGG) is not much studied. Methods We included 188 patients ≥18 years with IDH-mutated dLGG (WHO grade 2–3) histologically diagnosed between 2007–2020. Tissue microarrays of tumor samples for patients between 2007–2016 were used for immunodetection of Nestin, SOX2, SOX9, KLF4, NANOG, CD133 cMYC and Ki67. DNA methylation profile was used for stemness index (mDNAsi). Tumor contact with the SVZ was assessed and the distance was computed. Results Overall, 70.2% of the dLGG had SVZ contact. Tumors with SVZ contact were larger (102.4 vs. 30.9 ml, p<0.01), the patients were older (44.3 vs. 40.4 years, p=0.04) and more often had symptoms related to increased intracranial pressure (ICP) (31.8% vs. 7.1%, p<0.01). The expression of SOX2, SOX9, Nestin and Ki67 showed inter-sample variability, but no difference was found between tumors with or without SVZ contact, nor with the actual distance to the SVZ. mDNAsi was similar between groups (p=0.42). Conclusion We found no statistical relationship between proximity with the SVZ and mDNAsi or expression of SOX2, SOX9, Nestin and Ki67 in IDH-mutated dLGG. Our data suggests that the potential impact of SVZ on IDH-mutated dLGG is probably not associated with a more stemness-like tumor profile.

Targeting the neural stem cells in subventricular zone for the treatment of glioblastoma: an update from preclinical evidence to clinical interventions

“…The third layer consists of glial fibrillary acidic protein-positive astrocyte-like neural precursor cells (NPCs) and CD133-positive NSCs [ 15 ]. It is now believed that GBM originates from the accumulation of somatic mutations in NSCs in the SVZ [ 16 , 17 ]. SVZ has been shown to offer to GSCs a particular microenvironment participating in their resistance to chemoradiotherapy [ 18 ].…”

Deciphering the role of transcription factors in glioblastoma cancer stem cells

“…Transcription Factors in Glioblastoma Stem Cells and they coexpress stemness markers such as CD133, Sox2, and Nestin [19][20][21][22]. Conversely, GSCs differ from NSCs in their spectrum of gene mutations, chromosomal abnormalities, and tumorigenicity [23].…”