Molecular characteristics of single patient-derived glioma stem-like cells from primary and recurrent glioblastoma

Abstract

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro , SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan–Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro , PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.

ZDHHC15 promotes glioma malignancy and acts as a novel prognostic biomarker for patients with glioma

“…Furthermore, high ZDHHC15 expression was more prevalent in malignant glioma subtypes, including recurrence, IDH wild-type, and 1p/19q non-codeletion (Fig. 1 E-G), which are considered markers of a poor prognosis [ 26 , 27 ]. Conversely, there was no significant difference in ZDHHC15 mRNA expression among the three molecular subtypes of GBM and in the different methylation status of the MGMT promoter (Fig.…”

Preclinical Experimental Models for Human Glioma

“…Freshly isolated human glioma specimens in immunodeficient mice can recapitulate the most original salient features of primary tumors without any in vitro artificial selections (Liu et al, 2023;Vaubel et al, 2020). Immunocompromised mouse strains like nude mice, NOD/SCID mice, and NSG mice have been widely used to generate human glioma PDX models (Shi et al, 2022;Stringer et al, 2019;Wang et al, 2017). Moreover, the introduction of humanized mice has been reported to increase the PDX success rate.…”

“…For instance, co-expressing oncogene H-Ras and AKT and loss of p53 through Cre-LoxP-controlled lentiviral vectors in a small number of GFAP + cells have been shown to induce human high-grade gliomas in adult immunocompetent mice (Marumoto et al, 2009). Additionally, researchers have successfully developed the mutant IDH1-driven astrocytomas cooperated with clinically relevant gliomagenesis mutations and revealed that the de novo pyrimidine synthesis pathway is a potential therapeutic target in IDH1 mutant gliomas (Philip et al, 2018;Shi et al, 2022).…”