Potential Utility of Circulating MicroRNA-483 as a Biomarker for IGF-II-Associated Non-Islet Cell Tumor Hypoglycemia.

Abstract

In most cases of non-islet cell tumor hypoglycemia (NICTH), high molecular weight forms of insulin-like growth factor II, commonly referred to as big IGF-II, cause hypoglycemia. MicroRNA-483 (miR-483), encoded within an intron of IGF2, has been suggested to be coexpressed with IGF-II. The aim of this study is to demonstrate the utility and reliability of circulating miR-483 as a biomarker for diagnosis and therapeutic outcome of NICTH. Sera from 145 cases of suspected NICTH, and postoperative sera from 25 surgical cases of confirmed NICTH were subjected to Western blot analysis and enzyme-linked immunosorbent assay for IGF-II and quantitative polymerase chain reaction analysis for miR-483-5p and -3p. Tissue miR-483 expression levels were compared between resected solitary fibrous tumors (SFTs) and their surrounding margins from 11 surgical cases. NICTH was confirmed in 100 out of 145 cases based on the detection of big IGF-II in their sera. Receiver operating characteristic curve analysis revealed that serum miR-483-5p had a better diagnostic ability for NICTH than serum IGF-II or the classical diagnostic marker the IGF-II to IGF-I ratio. Notably, serum miR-483-5p levels decreased significantly with the disappearance of big IGF-II after surgical tumor resection. Tissue miRNA-483-5p and -3p expression levels were significantly higher in resected SFT tissues than in their surgical margins. Circulating miR-483-5p, derived from IGF-II-producing tumors, appears to be a more reliable biomarker for diagnosis and therapeutic outcome of NICTH than IGF-II or the IGF-II to IGF-I ratio. These findings highlight the clinical utility of miR-483-5p in the management of NICTH.