Endocrine Abstracts (2016) 46 P1 | DOI: 10.1530/endoabs.46.P1

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Helen C Miller1, Adam E Frampton1, Anna Malczewska1,2, Silvia Ottaviani1, Euan A Stronach1, Rashpal Flora3, Daniel Kaemmerer4, Gert Schwach5, Roswitha Pfragner5, Omar Faiz6, Beata Kos-Kudla2, George B Hanna7, Justin Stebbing1, Leandro Castellano1 & Andrea Frilling1

1Department of Surgery and Cancer, Imperial College, Hammersmith Hospital Campus, London, UK; 2Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland; 3Department of Histopathology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK; 4Zentralklinik Bad Berka GmbH, Robert-Koch-Allee, Bad Berka, Germany; 5Institute of Pathophysiology, Center for Molecular Medicine, Medical University of Graz, Graz, Austria; 6St Mark’s Hospital, Harrow, UK; 7Academic Surgical Unit, Department of Surgery and Cancer, Imperial College, St Mary’s Campus, London, UK.

Introduction: Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response.

Aim of the study: To profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers.

Material and methods: Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses.

Results: We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes.

Conclusion: Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA–mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted. (Work published).

Keywords: microRNAs, biomarkers, small bowel neuroendocrine tumour