Investigating microRNA-375 as a Tissue and Circulating Marker for Neuroendocrine Cells and Neoplasms
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Authors
Mayotte, Harrison R.
Date
Type
thesis
Language
eng
Keyword
miR-375 , neuroendocrine , neuroendocrine neoplasms , neuroendocrine differentiation , biomarker , NENs
Alternative Title
Abstract
Neuroendocrine neoplasia is an enigmatic disease that is currently without reliable diagnostic markers. Normal neuroendocrine cells are difficult to recognize upon routine H&E staining, requiring several IHC markers to confirm their cell-type. A lack of a single, specific marker has led to difficulties in successfully diagnosing neuroendocrine neoplasms (NENs), leading to poor patient outcomes. This has contributed to nearly 50% of cases becoming metastatic in the disease course. microRNAs (miRNA) are small non-coding RNA that negatively regulate gene expression through messenger RNA destabilization. Due to their disease specificity, miRNAs are being increasingly researched as potential candidate diagnostic markers. miRNA-375 (miR-375) was previously shown to be more highly expressed in NEN tissue compared to site matched controls using RNA sequencing. In this study, we investigate the potential for miR-375 to be used as a marker for neuroendocrine cell differentiation as well as neuroendocrine neoplasia. We first visualized miR-375 expression in healthy tissues from varying anatomical sites using chromogenic in situ hybridization. We found that miR-375 was only specific to candidate neuroendocrine cells, scattered throughout many tissues. The presence of miR-375 was then compared in neuroendocrine tumor tissue in organs of the gastroenteropancreatic system with non-neuroendocrine cancer from the same region. miR-375 was present in NEN tissue and absent in control tissues. Finally, we compared the plasma abundance of miR-375 in the circulation of lung-NEN patients to patients with non-NEN lung cancer and non-neoplastic lung disease. miR-375 abundance was found to be higher in the plasma of lung NEN patients compared to controls. With the results from this study, miR-375 has the potential to a be a promising candidate marker for future NEN diagnostics.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution 4.0 International
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution 4.0 International