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http://purl.uniprot.org/citations/37212470http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37212470http://www.w3.org/2000/01/rdf-schema#comment"

Background

The 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.

Methods

Immunoblotting, 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.

Results

Here, 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.

Conclusions

Inverse 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."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.org/dc/terms/identifier"doi:10.1002/cam4.6071"xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/author"White P."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/author"Perks C.M."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/author"Kurian K.M."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/author"Barber H.R."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/author"Harland A.J."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/name"Cancer Med"xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/pages"14426-14439"xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/title"Insulin-like growth factor binding protein-2 and glucose-regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH-wildtype glioblastoma patients."xsd:string
http://purl.uniprot.org/citations/37212470http://purl.uniprot.org/core/volume"12"xsd:string
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