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Poster Discussion – NETs and endocrine tumours

5891 - New circulating biomarkers in Gastro-Entero-Pancreatic-Neuroendocrine-Tumors

Date

30 Sep 2019

Session

Poster Discussion – NETs and endocrine tumours

Presenters

Martine Bocchini

Citation

Annals of Oncology (2019) 30 (suppl_5): v564-v573. 10.1093/annonc/mdz256

Authors

M. Bocchini1, M. Mazza1, F. Foca1, F. Nicolini1, R.A. Calogero2, S. Severi3, G. Paganelli3

Author affiliations

  • 1 Bioscience Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 - Meldola/IT
  • 2 Bioinformatics And Genomics Unit, MBC Centro di Biotecnologie Molecolari, 10126 - Torino/IT
  • 3 Nuclear Medicine & Radionuclide Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 - Meldola/IT

Resources

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Abstract 5891

Background

Gastro-Entero-Pancreatic-Neuroendocrine-Tumors (GEP-NETs) overexpresses Somatostatine receptors (SSTRs). Peptide Receptor Radionuclide Therapy (PRRT) target SSTRs. Although GEP-NETs show SSTRs overexpression, about 30% of patients do not respond to PRRT. It has been demonstrated that 18FDG –PET, reflects higher glucose uptake and represent a prognostic marker in GEP-NETs. MiRNAs are involved several mechanisms, including cell metabolism. In this scenario it would be pivotal to find new prognostic and/or predictive markers able to correlate with 18FDG/PET status.

Methods

Platelet free plasma from 66 GEP-NET patients was collected. Whole miRNOME NGS analysis was performed on exome enriched small-RNAs fraction of 24 patients: 12 18PET/FDG+ and 12 18PET/FDG-. MiRNAs significantly associated with 18PET/FDG outcome were identified and validated by RT/qPCR on overall case series. Target miRNAs fold enrichment were then combined to create predictors (pAB, pAC, pBC and pABC). Man-Whitney test was applied and validated miRNAs were correlated with clinical outcome and parameters (ki-67, grading, tumor burden and 68Gallium-PET SUVmax).

Results

NGS profiling revealed 7 miRNAs able to distinguish 18FDG/PET positive from negative Pancreatic-NETs (PNETs). Mir-A, mir-B, mir-C (patent pending) had been then validated on overall case series by multiplex RT/qPCR (p < 0,0109, p < 0,0033 and p < 0,0002, respectively) on PNETs case series and pBC resulted to be the best predictor (p < 0,0002). All validated miRNAs and derived predictors, expecially mir-B, result significantly increased in small intestine (SINETs) and in PNETs patients when compared to healthy controls. Correlation analysis between target miRNAs and clinical parameters also revealed that mir-B negatively correlates with 68Ga-PET SUVmax (p < 0,0351).

Conclusions

We defined a 3 miRNAs signature able to correlate with 18FDG/PET status. Over expression of mir-A, mir-B, mir-C or combined predictors in PNETs with the same SSTR status might help to identify PRRT non-responders. In addition mir-B negatively correlates with clinical outcome and 68Ga-PET SUVmax. We are investigating if mirB interfere with SSTR expression, affecting PRRT efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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