title: Enhanced expression of coproporphyrinogen oxidase in malignant brain tumors: CPOX expression and 5-ALA-induced fluorescence.
abstract: In photodynamic diagnosis, 5-aminolevulinic acid (5-ALA) is widely used for the fluorescence-guided resection of malignant brain tumors, where 5-ALA is converted to protoporphyrin IX, which exhibits strong fluorescence. Little is known, however, about the detailed molecular mechanisms underlying 5-ALA-induced fluorescence. To resolve this issue, we analyzed transcriptome profiles for the genes encoding enzymes, transporters, and a transcription factor involved in the porphyrin-biosynthesis pathway. By quantitative real-time (qRT)-PCR, we measured the mRNA levels of those genes in a total of 20 tumor samples that had been surgically resected from brain tumor patients at the Department of Neurosurgery of Osaka Medical College from 2008 to 2009. We selected 10 tumor samples with no 5-ALA-induced fluorescence, among which 2 were glioblastomas and 8 were metastatic brain tumors. Another 10 tumor samples were selected with strong fluorescence, among which 7 were glioblastomas and 3 were metastatic brain tumors. The qRT-PCR analysis study of these latter 10 samples revealed predominantly high levels of the mRNA of the coproporphyrinogen oxidase (CPOX) gene. The high mRNA level of CPOX expression was significantly well correlated with the phenotype of strong 5-ALA-induced fluorescence (P = .0003). These findings were further confirmed by immunohistochemical studies with a CPOX-specific antibody. It is concluded that induction of CPOX gene expression is one of the key molecular mechanisms underlying the 5-ALA-induced fluorescence of malignant brain tumors. The induction mechanism for the CPOX gene in brain tumors remains to be elucidated.
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Naokado
authors.initials: N
authors.lastname: Ikeda
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Kajimoto
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Miyatake
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hagiya
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Ogura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000556:secondary; D003304:Coproporphyrinogen Oxidase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005453:Fluorescence; D005909:Glioblastoma / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D059467:Transcriptome
chemical_list: D017319:Photosensitizing Agents; D012333:RNA, Messenger; D000622:Aminolevulinic Acid; D003304:Coproporphyrinogen Oxidase