Investigating microRNA-375 as a Tissue and Circulating Marker for Neuroendocrine Cells and Neoplasms

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Mayotte, Harrison R.
miR-375 , neuroendocrine , neuroendocrine neoplasms , neuroendocrine differentiation , biomarker , NENs
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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