miRNA Expression Profiling in G1 and G2 Pancreatic Neuroendocrine Tumors

Simple Summary Pancreatic neuroendocrine tumors are rare, but their incidence is rising. Several grades exist, and distinguishing between these is pivotal for clinical management. Currently, the grades can only be differentiated by histological analysis requiring invasive sampling. MicroRNAs are short non-protein coding RNA molecules that were shown to be differentially expressed in a wide variety of tumors. Here, we examined whether microRNAs could be exploited to differentiate grade 1 and 2 pancreatic neuroendocrine tumors and established significantly differentially expressed microRNAs.Abstract Pancreatic neuroendocrine neoplasms pose a growing clinical challenge due to their rising incidence and variable prognosis. The current study aims to investigate microRNAs (miRNA; miR) as potential biomarkers for distinguishing between grade 1 (G1) and grade 2 (G2) pancreatic neuroendocrine tumors (PanNET). A total of 33 formalin-fixed, paraffin-embedded samples were analyzed, comprising 17 G1 and 16 G2 tumors. Initially, literature-based miRNAs were validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), confirming significant downregulation of miR-130b-3p and miR-106b in G2 samples. Through next-generation sequencing, we have identified and selected the top six miRNAs showing the highest difference between G1 and G2 tumors, which were further validated. RT-qPCR validation confirmed the downregulation of miR-30d-5p in G2 tumors. miRNA combinations were created to distinguish between the two PanNET grades. The highest diagnostic performance in distinguishing between G1 and G2 PanNETs by a machine learning algorithm was achieved when using the combination miR-106b + miR-130b-3p + miR-127-3p + miR-129-5p + miR-30d-5p. The ROC analysis resulted in a sensitivity of 83.33% and a specificity of 87.5%. The findings underscore the potential use of miRNAs as biomarkers for stratifying PanNET grades, though further research is warranted to enhance diagnostic accuracy and clinical utility.