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Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas

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Title: Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas
Authors: Hou, Chongxian Browse this author
Yamaguchi, Shigeru Browse this author
Ishi, Yukitomo Browse this author
Terasaka, Shunsuke Browse this author →KAKEN DB
Kobayashi, Hiroyuki Browse this author →KAKEN DB
Motegi, Hiroaki Browse this author
Hatanaka, Kanako C. Browse this author
Houkin, Kiyohiro Browse this author →KAKEN DB
Keywords: 5-Aminolevulinic acid
Fluorescence-guided surgery
Protoporphyrin IX
Issue Date: Jun-2019
Publisher: Springer
Journal Title: Journal of neuro-oncology
Volume: 143
Issue: 2
Start Page: 197
End Page: 206
Publisher DOI: 10.1007/s11060-019-03158-3
PMID: 30929128
Abstract: Purpose5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) appears to be a promising treatment for glioma. However, 5-ALA-mediated fluorescence cannot always be detected in grade II/III gliomas. We hypothesized that gene expression patterns in the Protoporphyrin IX (PpIX) synthesis pathway may be associated with intraoperative fluorescence status of grade II/III gliomas, and then attempted to identify the key molecule of 5-ALA-mediated fluorescence.MethodsUsing 50 surgically obtained specimens, which were diagnosed as grade II and III gliomas, we analyzed gene expression within the PpIX synthesis pathway to identify candidate molecules according to intraoperative 5-ALA-mediated fluorescence status. The most likely candidate gene was selected and confirmed by protein expression analysis. To evaluate the biological function of the molecule in PpIX synthesis, functional analysis was performed using specific, small interference (si)RNA in the SW-1783human grade III glioma cell line.ResultsAmong the genes involved in the porphyrin synthesis pathway, the mRNA expression of Peptide transporter 2 (PEPT2) in FGS fluorescence-positive gliomas was significantly higher than that in fluorescence-negative gliomas. Protein expression of PEPT2 was also significantly higher in the fluorescence-positive gliomas, which was confirmed by western blot analysis and immunofluorescence analysis. The siRNA-mediated downregulation of the mRNA and protein expression of PEPT2 led to decreased PpIX fluorescence intensity, as confirmed by fluorescence spectrum analysis.ConclusionsThe results suggest PEPT2 is an important candidate molecule in 5-ALA-mediated FGS in grade II/III gliomas. As the overexpression of PEPT2 was associated with higher PpIX fluorescence intensity, PEPT2 may improve fluorescence-guided resection in grade II/III gliomas.
Rights: The final publication is available at
Type: article (author version)
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山口 秀

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