Investigation of MicroRNAs as predictors of radioligand therapy response in gastroenteropancreatic neuroendocrine tumours

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are commonly treated with radio-ligand therapy (RLT) but reliable biomarkers for predicting early disease progression are lacking. In this exploratory study we investigated whether microRNA (miRNA) expression in archival samples is associated with early response to RLT and with tumour origin and grading. Forty-eight formalin-fixed, paraffin-embedded samples from G1–G2 GEP-NETs patients treated with RLT (177Lu-Oxodotreotide (Lutathera®) were analyzed. Two CT or MRI scans per patient, performed within three months before and after RLT, were used to assess early progression (PD) according to RECIST v1.1. Thirteen miRNAs previously implicated in NET biology were quantified by qRT-PCR. Multiple logistic regression evaluated associations between miRNA expression and early progression, as well as relationships with tumour origin and grade. We observed trends suggesting that lower expression of miR-21-5p (OR = 0.51, 90% CI: 0.26–1.00) and miR-196a (OR = 0.78, 90% CI: 0.59–1.02), and higher expression of miR‑30a-5p (OR = 2.62, 90% CI: 0.1.14–6.05) may be associated with a reduced likelihood of early progression. Lower miR-196a and higher miR‑30a-5p expression was also more frequent in pancreatic tumours and lower miR-196a expression is associated to G1 lesions. These findings indicate that miRNA profiling in GEP-NETs archival samples is feasible and support the potential role of miR-21-5p, miR-196a, and miR‑30a-5p as exploratory biomarkers for early progression afterRLT. Further validation in independent cohorts is required to confirm these preliminary observations.