Evidence map›Paper›PMID 37212470›Full record

ArticleCancer medicine2023

Insulin-like growth factor binding protein-2 and glucose-regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH-wildtype glioblastoma patients.

Abigail J Harland, Claire M Perks, Paul White, Kathreena M Kurian, Hannah R Barber

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

5 citing papers in PubMed, 3 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

5 authors at 3 institutions in 1 country.

Abigail J HarlandBrain Tumour Research Centre, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0001-7749-1424
Claire M PerksIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK.ORCID 0000-0003-1562-891X
Paul WhiteFaculty of Health Sciences, University of the West England, Bristol, UK.ORCID 0000-0002-7503-9896
Kathreena M KurianBrain Tumour Research Centre, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0003-0303-3716
Hannah R BarberBrain Tumour Research Centre, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-6619-1001
At Bristol · GBSouthmead Hospital · GBUniversity of the West of England · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe overall survival of IDH-wildtype glioblastoma patients is poor despite best available treatments. There is an urgent need for new biomarkers to inform more precise disease stratification. Previous studies have identified insulin-like growth factor binding protein-2 (IGFBP-2) as a potential biomarker for glioblastoma diagnosis and therapeutic targeting. Other studies have indicated links between the insulin-like growth factor (IGF) axis and tumorigenic functions of a molecular chaperone glucose related protein of 78 kDa (GRP78). We aimed to interrogate the oncogenic effects of IGFBP-2 and GRP78 in our glioma stem cell (GSC) lines and clinical cohort.

methodsImmunoblotting, reverse transcription quantitative real-time PCR were used to quantify protein and mRNA levels derived from GSCs and non-malignant neural stem cells (NSCs). Microarray analysis was used to compare the differences in IGFBP-2 (IGFBP-2) and GRP78 (HSPA5) transcript expression between NSCs, GSCs and adult human cortex samples. Immunohistochemistry was used to quantify IGFBP-2 and GRP78 expression in IDH-wildtype glioblastoma tissue sections (n = 92) and clinical implications assessed using survival analysis. Finally, the relationship between IGFBP-2 and GRP78 was further explored molecularly using coimmunoprecipitation.

resultsHere, we demonstrate that IGFBP-2 and HSPA5 mRNA is overexpressed in GSCs and NSCs in comparison to non-malignant brain tissue. We also determined a relationship in which G144 and G26 GSCs expressed higher IGFBP-2 protein and mRNA than GRP78, and this was reversed in mRNA isolated from adult human cortex samples. Clinical cohort analysis revealed that Glioblastomas with high IGFBP-2 protein expression paired with low GRP78 protein expression were significantly associated with a much shorter survival time (Median = 4 months, p = 0.019) compared with 12-14 months for any other combination of high/low protein expression.

conclusionsInverse levels of IGFBP-2 and GRP78 may be adverse clinical prognostic markers in IDH-wildtype glioblastoma. Further interrogation of the mechanistic link between IGFBP-2 and GRP78 may be important for rationalisation of their potential as biomarkers and therapeutic targets.

Indexed as

GlioblastomaAdultBiomarkersEndoplasmic Reticulum Chaperone BiPHumansInsulin-Like Growth Factor Binding Protein 2Insulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor IIsocitrate DehydrogenasePrognosisRNA, MessengerBiomarkersEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanIDH1 protein, humanIGFBP2 protein, humanInsulin-Like Growth Factor Binding Protein 2Insulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor IIsocitrate DehydrogenaseRNA, Messengerbiomarkerscancer stem cellsprognosissurvival

Identifiers

PMID37212470
PMCPMC10358216
OpenAlexW4377220318

What OpenQuestion holds

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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.