Benefit and limitations of glioblastoma tissue slice cultures – an RNA sequencing study

ABSTRACT: One of the major challenges in cancer research is to find models closely resembling the tumor within patients. Human tissue slice cultures represent a promising approach to display the patient's biology ex vivo. Recently, it was shown that these slices can be successfully analyzed by whole transcriptome sequencing as well as automated histochemistry, increasing their usability as preclinical model. Glioblastoma multiforme (GBM) is a highly malignant brain tumor with poor prognosis and little is known about its genetic background and heterogeneity regarding therapy success. In this study, tissue of 25 patients with primary GBM were processed into slice cultures and treated with standard therapy (irradiation and temozolomide). Total RNA sequencing and automated histochemistry were performed to display treatment-mediated effects at a transcriptional and histological level. Slice cultures from long-term survivors (OS > 24 months) exhibited higher apoptosis than cultures from patients with shorter OS. Proliferation within these slices was slightly increased in contrast to other groups, but not significant. Among all samples, 58 protein-coding genes were upregulated and 32 downregulated in treated vs. untreated slice cultures. In general, an upregulation of DNA damage-related and cell cycle checkpoint genes as well as enrichment of genotoxicity pathways and p53-dependent signaling was found after treatment. In conclusion, we demonstrate that treatment-mediated effects in GBM slice cultures can be determined by RNA sequencing and histological staining. The slice culture model reproduces knowledge from former studies regarding transcriptomic changes and its applicability is further improved by a comprehensible correlation with survival data of the patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179649 | GEO | 2022/02/09

REPOSITORIES: GEO