Metb-02. Expression Level of Glutaminase 2 Is Associated With Regional Heterogeneity of 5-aminolevulinic Acid Fluorescence in Glioblastoma
Year: 2016
Type: conference-abstract
Abstract: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a widely used for glioblastoma (GBM) treatment. However, there is intratumoral heterogeneity of fluorescence intensity which may reflect different onco-metabolic program. We investigated the genes that is responsible for the 5-ALA fluorescence intensity in GBM tissue. We have developed the in-house system of fluorescence quantification in tumor tissues. Using this system, we collected 3 classes of GBM tissues in each of 5 patients according to the fluorescence intensity such as strong, weak, and none, during the 5-ALA fluorescence-guided surgery. After RNA extraction from all 15 samples, gene expression profiles were analyzed by RNA-sequencing. We identified 77 genes of proportional relation and 509 genes of inverse relation between gene expression and fluorescence intensity. Gene set enrichment analysis was performed with the identified differentially expressed genes, and we focused on glutaminase 2 (GLS2) gene, because it was derived in multiple significant gene sets of cell metabolism. Higher expression of GLS2 is related lower 5-ALA fluorescence. We validated the effect of GLS2 on 5-ALA fluorescence in multiple GBM cell lines. After transduction of GLS2 gene into U87MG and T98 cell lines, we could observe significant reduction of intracellular protoporphyrinogen IX level after 5-ALA treatment. We discovered an inverse relationship between 5-ALA fluorescence and GLS2 expression in GBM, which can be a metabolic surrogate marker for the degree of malignancy in the realm of intratumoral heterogeneity.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2589082157