Abstract #16

by | Sep 18, 2023 | 2023 Abstracts

Abstract 16- 0815-0830
Category: Basic Science

At the end of the session, participants will be able to:

  1. Discuss the role of neurotransmission molecules regarding glioblastoma development and survival.
  2. Recognize informatic tools utilized for both cellular identification in single-cell RNAseq experiments and digital slide analysis, which may improve the speed and quality of their research pipeline.

COI Disclosure:

None to disclose

Presenter

Raul Cotau is a dedicated fourth-year medical student at Laval University on a journey to advance knowledge in the fields of cancer research, and next-generation sequencing. Fond of interdisciplinarity, Raul proactively decided to acquire proficiency in multiple programming languages before pursuing a master’s in molecular medicine. This endeavor prepared him to effectively analyze complex genetic and visual data.
His passion for his work has earned him numerous awards and established his reputation as a diligent and efficient student. Raul aspires to contribute to the enhancement of clinical practices through his academic and professional journey, all while inspiring others to explore additional areas of study.

Authors

Raul Cotau 1234, Étienne Audet-Walsh 145, Maxime Richer 36

1 Department of molecular medicine, Université Laval, Québec, Canada

2 Department of medicine, Université Laval, Québec, Canada

3 Neuroscience axis, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada

4 Cancer research center, Université Laval, Québec, Canada

5 Endocrinology and nephrology axis, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada

6 Department of molecular biology, medical biochemistry, and pathology, Université Laval, Québec, Canada

    Target Audience:

    Pathologists, Residents, Medical Students

    CanMEDS:
    Scholar

    Study of gamma-aminobutyric acid and glutamate signaling pathways in glioblastoma

    Abstract

    Glioblastomas (GBM) represent the majority of malignant primary brain tumors, and cannot be cured. The identification of their survival- and proliferation-associated mechanisms may help introduce new therapeutic targets. Several lines of evidence suggest that neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are involved in gliomagenesis. Their signaling pathways within the tumor microenvironment (TME) remain nonetheless poorly defined. We hypothesize that the modulation of GABA and glutamate genes may control tumoral aggressivity. We (1) identify vulnerable biomarker genes for GBM (stage IV glioma), and (2) assess their validity in in vitro and clinical studies. A GABA-treated U87 GBM cell line was bulk RNA sequenced, and single-cell RNA-seq data of 9 resected new-diagnostic, and 5 recurrent IDH-wildtype GBM allowed for differential and enrichment analysis. Data suggested that GABA regulates cancer-associated pathways, such as survival, and metabolism. Using a novel algorithmic cell type identification approach, GBM cells, along with neuroimmune pro- and anti-inflammatory populations were identified. Potential GABA, glutamate, and calcium neurotransmitter-associated biomarkers previously identified in the laboratory were found to be differentially expressed between cell-group clusters. Further enrichment aims to identify cell types, and genes associated with protumoral activity. A cohort comprising 50 resected GBM samples was utilized to associate those new genes, as well as previous markers C5AR1, VGAT, GAD–1, and GABA-B to histologic characteristics including necrosis, angiogenesis, and infiltration. Immunohistochemical alignment between our, and clinical markers (ex. MIB1 for proliferation) was performed. GABA was significantly overexpressed in MIB1-rich zones. This study introduces GABA- and glutamate-associated biomarkers as potential GBM therapeutic vulnerabilities.