Abstract:
:Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is now a widely-used modality for glioblastoma (GBM) treatment. However, intratumoral heterogeneity of fluorescence intensity may reflect different onco-metabolic programs. Here, we investigated the metabolic mechanism underlying the heterogeneity of 5-ALA fluorescence in GBM. Using an in-house developed fluorescence quantification system for tumor tissues, we collected 3 types of GBM tissues on the basis of their fluorescence intensity, which was characterized as strong, weak, and none. Expression profiling by RNA-sequencing revealed 77 genes with a proportional relationship and 509 genes with an inverse relationship between gene expression and fluorescence intensity. Functional analysis and in vitro experiments confirmed glutaminase 2 (GLS2) as a key gene associated with the fluorescence heterogeneity. Subsequent metabolite profiling discovered that insufficient NADPH due to GLS2 underexpression was responsible for the delayed metabolism of 5-ALA and accumulation of protoporphyrin IX (PpIX) in the high fluorescence area. The expression level of GLS2 and related NADPH production capacity is associated with the regional heterogeneity of 5-ALA fluorescence in GBM.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Kim S,Kim JE,Kim YH,Hwang T,Kim SK,Xu WJ,Shin JY,Kim JI,Choi H,Kim HC,Cho HR,Choi A,Chowdhury T,Seo Y,Dho YS,Kim JW,Kim DG,Park SH,Kim H,Choi SH,Park S,Lee SH,Park CKdoi
10.1038/s41598-017-12557-3subject
Has Abstractpub_date
2017-09-22 00:00:00pages
12221issue
1issn
2045-2322pii
10.1038/s41598-017-12557-3journal_volume
7pub_type
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