Evidence map›Paper›PMID 35665365›Full record

ArticleFrontiers in medicine2022

Heme Biosynthesis Factors and 5-ALA Induced Fluorescence: Analysis of mRNA and Protein Expression in Fluorescing and Non-fluorescing Gliomas.

Mario Mischkulnig, Thomas Roetzer-Pejrimovsky, Daniela Lötsch-Gojo, Nina Kastner, Katharina Bruckner, Romana Prihoda, Alexandra Lang, Mauricio Martinez-Moreno, Julia Furtner, Anna Berghoff and 4 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Mario MischkulnigDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Thomas Roetzer-PejrimovskyComprehensive Cancer Center-Central Nervous System Tumours Unit, Medical University of Vienna, Vienna, Austria.
Daniela Lötsch-GojoDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Nina KastnerDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Katharina BrucknerDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Romana PrihodaDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Alexandra LangDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Mauricio Martinez-MorenoDepartment of Neurosurgery, Vivantes Klinikum Neukölln, Berlin, Germany.
Julia FurtnerComprehensive Cancer Center-Central Nervous System Tumours Unit, Medical University of Vienna, Vienna, Austria.
Anna BerghoffComprehensive Cancer Center-Central Nervous System Tumours Unit, Medical University of Vienna, Vienna, Austria.
Adelheid WoehrerComprehensive Cancer Center-Central Nervous System Tumours Unit, Medical University of Vienna, Vienna, Austria.
Walter BergerInstitute of Cancer Research, Medical University of Vienna, Vienna, Austria.
Georg WidhalmDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Barbara KieselDepartment of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Medical University of Vienna · ATComprehensive Cancer Center Vienna · ATVivantes Klinikum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: The intraoperative visualization of adult-type diffuse gliomas with 5-aminolevulinic acid (5-ALA) induced fluorescence is widely used in the neurosurgical field. While visible 5-ALA induced fluorescence is found in the majority of high-grade gliomas, most low-grade gliomas lack visible fluorescence during surgery. Recently, the heme biosynthesis pathway was identified as crucial influencing factor for presence of visible fluorescence since it metabolizes 5-ALA to fluorescing Protoporphyrin IX (PpIX). However, the exact alterations within the heme biosynthesis pathway resulting in visible 5-ALA induced fluorescence in gliomas are still unclear. The aim of the present study was thus to compare the mRNA and protein expression of promising intramitochondrial heme biosynthesis enzymes/transporters in glioma tissue samples of different fluorescence behavior. Methods: A total of 19 strongly fluorescing and 21 non-fluorescing tissue samples from neurosurgical adult-type diffuse gliomas (WHO grades II-IV) were included in the current analysis. In these samples, we investigated the mRNA expression by quantitative real time PCR and protein expression using immunohistochemistry of the intramitochondrial heme biosynthesis enzymes Coproporphyrinogen Oxidase (CPOX), Protoporphyrinogen Oxidase (PPOX), Ferrochelatase (FECH), and the transporter ATP-binding Cassette Subfamily B Member 2 (ABCG2). Results: Regarding mRNA expression analysis, we found a significantly decreased ABCG2 expression in fluorescing specimens compared to non-fluorescing samples ( Conclusion: Distinct alterations of the analyzed heme biosynthesis factors were found primarily on protein level. Our data indicate that heme biosynthesis pathway activity in general is enhanced in fluorescing gliomas with upregulation of PpIX generating enzymes and decreased ABCG2 mediated PpIX efflux outweighing the also increased further metabolization of PpIX to heme. Intramitochondrial heme biosynthesis factors thus constitute promising pharmacological targets to optimize intraoperative 5-ALA fluorescence visualization of usually non-fluorescing tumors such as low-grade gliomas.

Indexed as

5-ALAfluorescencegliomasheme biosynthesismRNA expressionprotein expression

Identifiers

PMID35665365
PMCPMC9157484
OpenAlexW4280627301

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.