51. Glutaminase 2 expression is associated with regional heterogeneity of 5-aminolevulinic acid fluorescence in glioblastoma
- Author
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Yun Sik Dho, Jong Yeon Shin, Anna Choi, Taeyoung Hwang, Jong Il Kim, Se-Hoon Lee, Sung Kwon Kim, Jin Wook Kim, Chul-Kee Park, Sojin Kim, Hye Rim Cho, Hyoungseon Choi, Sung Hye Park, Wen Jun Xu, Hyeonjin Kim, Youngbeom Seo, Tamrin Chowdhury, Hee Chan Kim, Sunghyouk Park, Seung Hong Choi, Ja Eun Kim, Dong Gyu Kim, and Yong Hwy Kim
- Subjects
0301 basic medicine ,lcsh:Medicine ,Protoporphyrins ,Biology ,Fluorescence ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glutaminase ,Cell Line, Tumor ,Gene expression ,Humans ,Prospective Studies ,lcsh:Science ,Gene ,Fluorescent Dyes ,Multidisciplinary ,Protoporphyrin IX ,Brain Neoplasms ,Gene Expression Profiling ,lcsh:R ,Metabolism ,Molecular biology ,In vitro ,Levulinic Acids ,Gene expression profiling ,030104 developmental biology ,chemistry ,Surgery, Computer-Assisted ,Cell culture ,030220 oncology & carcinogenesis ,lcsh:Q ,Glioblastoma ,NADP - 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.
- Published
- 2017