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CYPA and CD147 expression analysis in human glioblastoma: Evidence for a correlation with reduced survival

Matthews, V., Candy, P.A., West, K.A.ORCID: 0000-0002-7036-5334, Knuckey, N.W., Robbins, P., Jeffcote, T. and Boulos, S. (2018) CYPA and CD147 expression analysis in human glioblastoma: Evidence for a correlation with reduced survival. Journal of Translational Science, 4 (5). pp. 1-7.

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Glioblastomas (GBMs) are fatal WHO grade IV astrocytomas with a median survival of 14.6 months. Immunohistochemical (IHC) studies indicate that cyclophilin A (CYPA), and its receptor CD147 are elevated in GBM, but the impacts on disease progression are poorly understood. We determined their occurrence in diffuse astrocytomas (WHO grades II-IV) using IHC and evaluated how gene expression affects patient outcomes in The Cancer Genome Atlas (TCGA) and REMBRANDT datasets (GBM and Low-Grade-Glioma: LGG). While IHC staining of CYPA was evident across all tumour grades, CD147 staining increased with tumour grade. However, while analysis of the TCGA grade II/III tumour dataset showed a trend towards high CD147 gene expression and reduced patient survival (HR=2.34, p=0.064, n=132), the results were not statistically significant. By contrast, analysis of the TCGA GBM dataset showed that high CYPA expression was significantly associated with reduced survival (HR=1.30, p=0.009; n=593). Furthermore, Kaplan-Meier analysis of both the TCGA and REMBRANDT (p=0.052; n=176) GBM datasets showed a comparable reduction in survival of about 3-months for patients with high CYPA expression. We found that CYPA gene amplification (≥2.2 copies) occurred in 72% of patients (REMBRANDT GBM dataset) and was correlated with reduced survival (log-rank p = 0.022). Finally, we observed a correlation between CYPA and CD147 gene expression in grade II/III (R=0.481, p=1.81x10-6) and grade IV (R=0.132; p=0.0012) tumours. Together, our data identify CYPA and CD147 as potential pathogenic determinants in glioblastoma.

Item Type: Journal Article
Publisher: OA Text
Copyright: ©2018 Matthews V.
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