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

Hou, Chongxian; Yamaguchi, Shigeru; Ishi, Yukitomo; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Motegi, Hiroaki; Hatanaka, Kanako C.; Houkin, Kiyohiro

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

Hou, Chongxian; Yamaguchi, Shigeru; Ishi, Yukitomo et al.

Journal of neuro-oncology, 2019, 143(2), 197-206

Permalink : https://hdl.handle.net/2115/78256

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/78256
タイトル	Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas
著者	Hou, Chongxian ; Yamaguchi, Shigeru ; Ishi, Yukitomo ; Terasaka, Shunsuke ; Kobayashi, Hiroyuki ; Motegi, Hiroaki ; Hatanaka, Kanako C. ; Houkin, Kiyohiro
著者名 Hou, Chongxian
著者名 Yamaguchi, Shigeru
著者名 Ishi, Yukitomo
e-Rad_Researcher 10447055 著者名 Terasaka, Shunsuke
e-Rad_Researcher 70374478 著者名 Kobayashi, Hiroyuki
著者名 Motegi, Hiroaki
著者名 Hatanaka, Kanako C.
e-Rad_Researcher 90229146 著者名 Houkin, Kiyohiro
言語	英語
キーワード	5-Aminolevulinic acid
	Glioma
	Fluorescence-guided surgery
	Protoporphyrin IX
発行日	2019-06
出版者	Springer
収録物名	Journal of neuro-oncology
巻(号)	143(2)
ページ	197-206
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	The final publication is available at link.springer.com
PISSN	0167-594X
関連情報	PMID 30929128
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s11060-019-03158-3