Glutaminase 2 expression is associated with regional heterogeneity of 5-aminolevulinic acid fluorescence in glioblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Sojin Kim, Ja Eun Kim, Yong Hwy Kim, Taeyoung Hwang, Sung Kwon Kim, Wen Jun Xu, Jong-Yeon Shin, Jong-Il Kim, Hyoungseon Choi, Hee Chan Kim, Hye Rim Cho, Anna Choi, Tamrin Chowdhury, Youngbeom Seo, Yun-Sik Dho, Jin Wook Kim, Dong Gyu Kim, Sung-Hye Park, Hyeonjin Kim, Seung Hong Choi, Sunghyouk Park, Se-Hoon Lee, Chul-Kee Park

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. More... »

PAGES

12221

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-12557-3

DOI

http://dx.doi.org/10.1038/s41598-017-12557-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091849544

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28939850


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