Abstract
Oral squamous cell carcinoma (OSCC) is a common malignancy for which there is poor prognosis and limited therapeutic options. The objective was to identify mRNA targets of dysregulated miRNAs in OSCC using integrated analysis and understand molecular abnormality in surgical margins. We used biopsies along the spatial axis from normal tissue defined by narrow band imaging (NBI) through conventional white light (WL) margins to tumour from 18 patients undergoing surgical resection for OSCC. Overall 119 miRNA and 4794 mRNA were differentially expressed along the adjacent normal tissue to tumour axis. Analysis of miRNA profiles demonstrated the NBI margins were molecularly distinct from both the tumour and WL margin. Integrated analysis identified 193 miRNA-mRNA interactions correlated to the spatial axis of NBI-WL-T. We used cross-validation analysis to derive a spatial interactome signature of OSCC comprising 100 putative miRNA-mRNA interactions between 40 miRNA and 96 mRNA. Bioinformatic analysis suggests that miRNA dysregulation in OSCC may contribute to activation of the oncostatin M, BDNF and TGF-β pathways. Our data demonstrates that surgical margins defined by NBI leave less potentially malignant residual tissue. The miRNA-mRNA interactome provides insight into dysregulated miRNA signalling in OSCC and supports molecular definition of tumour margins.
Highlights
Integrated miRNA-mRNA spatial signature for oral squamous cell carcinoma: a prospective profiling study of Narrow Band Imaging guided resection
This study has shown that miRNA differential expression, putative miRNA-mRNA interactions and dysregulated biological signalling are greater in T vs narrow band imaging (NBI) than in T vs white light (WL)
Our analysis across the three biopsy sites strongly supports our premise that resection of Oral squamous cell carcinoma (OSCC) to surgical margins that are determined by NBI rather than by WL
Summary
Integrated miRNA-mRNA spatial signature for oral squamous cell carcinoma: a prospective profiling study of Narrow Band Imaging guided resection. The objective was to identify mRNA targets of dysregulated miRNAs in OSCC using integrated analysis and understand molecular abnormality in surgical margins. We used biopsies along the spatial axis from normal tissue defined by narrow band imaging (NBI) through conventional white light (WL) margins to tumour from 18 patients undergoing surgical resection for OSCC. Our data demonstrates that surgical margins defined by NBI leave less potentially malignant residual tissue. We reported that use of Narrow Band Imaging for pre-operative OSCC assessment led surgeons to resect visually normal tissue that harboured significant molecular abnormalities without increasing the surgical field unnecessarily, and significantly decreased locoregional recurrence[7]. Their link to cancer is strengthened by the clustering of miRNA loci within the genome, often
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