Abstract
Background
Improved treatment of glioblastoma (GBM) needs to address tumor invasion, a hallmark of the disease that remains poorly understood. In this study, we profiled GBM invasion through integrative analysis of histological and single-cell RNA sequencing (scRNA-seq) data from ten patients.
Methods
Human histology samples, patient-derived xenograft mouse histology samples, and scRNA-seq data were collected from ten GBM patients. Tumor invasion was characterized and quantified at the phenotypic level using H&E and Ki-67 histology stains. Crystallin alpha B (CRYAB) and CD44 were identified as regulators of tumor invasion from scRNA-seq transcriptomic data and validated
in vitro,
in vivo, and in a mouse GBM resection model.
Results
At the cellular level, we found that invasive GBM are less dense and proliferative than their non-invasive counterparts. At the molecular level, we identified unique transcriptomic features that significantly contribute to GBM invasion. Specifically, we found that CRYAB significantly contributes to post-operative recurrence and is highly co-expressed with CD44 in invasive GBM samples.
Conclusions
Collectively, our analysis identifies differentially expressed features between invasive and nodular GBM, and describes a novel relationship between CRYAB and CD44 that contributes to tumor invasiveness, establishing a cellular and molecular landscape of GBM invasion.
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