Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma

Kruthika, Banavathy S and Jain, Ruchi and Arivazhagan, A and Bharath, RD and Yasha, TC and Kondaiah, Paturu and Santosh, Vani (2019) Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma. In: JOURNAL OF NEURO-ONCOLOGY, 141 (2). pp. 315-325.

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Abstract

PurposePeritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT.Methods17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach.ResultsUnsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment.ConclusionsWe show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.

Item Type:	Journal Article
Publication:	JOURNAL OF NEURO-ONCOLOGY
Publisher:	SPRINGER
Additional Information:	Copyright of this article belongs to SPRINGER
Keywords:	GBM; Peritumoural brain zone; Gene expression profile; PBK; Recurrence
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	14 Feb 2019 05:57
Last Modified:	14 Feb 2019 05:57
URI:	http://eprints.iisc.ac.in/id/eprint/61715

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