Differential gene expression in peritumoral brain zone of glioblastoma: role of SERPINA3 in promoting invasion, stemness and radioresistance of glioma cells and association with poor patient prognosis and recurrence.

Autor: Nimbalkar VP; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Kruthika BS; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Sravya P; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Rao S; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Sugur HS; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Verma BK; Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, 560012, India., Chickabasaviah YT; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Arivazhagan A; Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India., Kondaiah P; Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, 560012, India., Santosh V; Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India. vani.santosh@gmail.com.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2021 Mar; Vol. 152 (1), pp. 55-65. Date of Electronic Publication: 2021 Jan 03.
DOI: 10.1007/s11060-020-03685-4
Abstrakt: Purpose: Glioblastoma (GBM) is a highly invasive tumor. Despite advances in treatment modalities, tumor recurrence is common, seen mainly in the peritumoral brain zone (PBZ). We aimed to molecularly characterize PBZ, to understand the pathobiology of tumor recurrence.
Methods/patients: We selected eight differentially regulated genes from our previous transcriptome profiling study on tumor core and PBZ. Expression of selected genes were validated in GBM (tumor core and PBZ, n = 37) and control (n = 22) samples by real time quantitative polymerase chain reaction (qPCR). Serine protease inhibitor clade A, member 3 (SERPINA3) was selected for further functional characterization in vitro by gene knockdown approach in glioma cells. Its protein expression by immunohistochemistry (IHC) was correlated with other clinically relevant GBM markers, patient prognosis and tumor recurrence.
Results: The mRNA expression of selected genes from the microarray data validated in tumor core and PBZ and was similar to publicly available databases. SERPINA3 knock down in vitro showed decreased tumor cell proliferation, invasion, migration, transition to mesenchymal phenotype, stemness and radioresistance. SERPINA3 protein expression was higher in PBZ compared to tumor core and also was higher in older patients, IDH wild type and recurrent tumors. Finally, its expression showed positive correlation with poor patient prognosis.
Conclusions: SERPINA3 expression contributes to aggressive GBM phenotype by regulating pro-tumorigenic actions in vitro and is associated with adverse clinical outcome.
Databáze: MEDLINE
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