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MiRNA-3653 Is a Potential Tissue Biomarker for Increased Metastatic Risk in Pancreatic Neuroendocrine Tumours

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Abstract

Pancreatic neuroendocrine tumours (PNETs) are relatively uncommon, accounting for 1–2% of all pancreatic neoplasms. Tumour grade (based on the Ki67 proliferative index and mitotic rate) is associated with metastatic risk across large cohorts; however, predicting the behaviour of individual tumours can be difficult. Therefore, any tool which could further stratify metastatic risk may be clinically beneficial. We sought to investigate microRNA (miRNA) expression as a marker of metastatic disease in PNETs. Tumours from 37 patients, comprising 23 with locoregional disease (L) and 14 with distant metastases (DM), underwent miRNA profiling. In total 506 miRNAs were differentially expressed between the L and DM groups, with four miRNAs (miR-3653 upregulated, and miR-4417, miR-574-3p and miR-664b-3p downregulated) showing statistical significance. A database search demonstrated that miRNA-3653 was associated with ATRX abnormalities. Mean survival between the two groups was correlated with mean expression of miRNA-3653; however, this did not reach statistical significance (p = 0.204). Although this is a small study, we conclude that miRNA-3653 upregulation may be associated with an increased risk of metastatic disease in PNETS, perhaps through interaction with ATRX and the alternate lengthening of telomeres pathway.

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Funding

This project was fully funded by a grant awarded to Preetjote Gill and Jaswinder Samra by Ipsen Pty Ltd. A/Prof Roderick Clifton-Bligh has received speaker honoraria from AMGEN, EISAI and IPSEN. The other authors have no relevant funding sources or conflicts of interests to declare.

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Author notes

  1. Anthony J. Gill and Jaswinder S. Samra contributed equally to this work.

Authors and Affiliations

  1. Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia

    Preetjote Gill, Terence C. Chua, Christopher B. Nahm, Anubhav Mittal & Jaswinder S. Samra

  2. Sydney Medical School, University of Sydney, Sydney, Australia

    Edward Kim, Roderick J. Clifton-Bligh, Christopher B. Nahm, Anubhav Mittal, Anthony J. Gill & Jaswinder S. Samra

  3. Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia

    Edward Kim & Roderick J. Clifton-Bligh

  4. Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, 2065, Australia

    Roderick J. Clifton-Bligh

  5. Australian Pancreatic Centre, St Leonards, Sydney, Australia

    Christopher B. Nahm, Anubhav Mittal, Anthony J. Gill & Jaswinder S. Samra

  6. NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia

    Anthony J. Gill

  7. Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia

    Anthony J. Gill

  8. Faculty of Medical and Health Sciences, Macquarie University, Sydney, Australia

    Jaswinder S. Samra

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  1. Preetjote Gill
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Corresponding authors

Correspondence to Anthony J. Gill or Jaswinder S. Samra.

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Conflict of Interest

Author Preetoje Gill declares that she has received a research grant from IPSEN which supported this study.

Author Edward Kim declares that he has no conflict of interest.

Author Terrence Chua declares that he has no conflict of interest.

Author Roderick Clifton-Bligh has received speaker honoraria from AMGEN, EISAI and IPSEN.

Author Christpher Nahm declares that he has no conflict of interest.

Author Anubhav Mittal declares that he has no conflict of interest.

Author Anthony Gill declares that he has no conflict of interest.

Author Jaswinder Samra declares that he has received a research grant from IPSEN which supported this study.

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Gill, P., Kim, E., Chua, T.C. et al. MiRNA-3653 Is a Potential Tissue Biomarker for Increased Metastatic Risk in Pancreatic Neuroendocrine Tumours. Endocr Pathol 30, 128–133 (2019). https://doi.org/10.1007/s12022-019-9570-y

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  • DOI: https://doi.org/10.1007/s12022-019-9570-y

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