miRNA Expression Profiling in G1 and G2 Pancreatic Neuroendocrine Tumors.

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.