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30.03.2019 | Laboratory Investigation

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

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

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2019

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Abstract

Purpose

5-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.

Methods

Using 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-1783 human grade III glioma cell line.

Results

Among 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.

Conclusions

The 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.

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Titel: Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas
verfasst von: Chongxian Hou
Shigeru Yamaguchi
Yukitomo Ishi
Shunsuke Terasaka
Hiroyuki Kobayashi
Hiroaki Motegi
Kanako C. Hatanaka
Kiyohiro Houkin
Publikationsdatum: 30.03.2019
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 2/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03158-3

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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

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

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