Clinical application of microRNA testing in neuroendocrine tumors of the gastrointestinal tract

Abstract

It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal tumors including gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs are a heterogeneous group of epithelial neoplasms with neuroendocrine differentiation. At present, early detection and surgical resection of GEP-NETs represent the best chance for a cure. Thus, clinically useful biomarkers for GEP-NETs that strongly correlate with early detection are urgently needed. The purpose of this review is to summarize the role of miRNAs in GEP-NET carcinogenesis and their possible use as novel diagnostic, prognostic and predictive biomarkers.

Figure 1

Overview of the different molecular techniques applied in the study of miRNA dysregulation in human pathology. All techniques could be applied to tissue sample (red circle; both fresh and formalin-fixed paraffin-embedded) and body fluids samples (blue circle; mainly urine and plasma).

Figure 2

miR-21 is significantly overexpressed in pancreatic neuroendocrine tumors and it is detectable in patients’ plasma samples. (A) Pancreatic neuroendocrine tumors (PanNETs) usually show a significantly higher miR-21 expression in comparison to normal pancreatic Langerhans islets (qRT-PCR). This overexpression is confirmed by in situ hybridization (upper panel: a PanNET showing strong miR-21 staining; lower panel: same case stained with the positive control U6). (B) In PanNET patients, circulating cell-free plasma miR-21 is overexpressed in comparison to chronic pancreatitis patients and could be used as a novel diagnostic biomarker.