Context: 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 gene, has been suggested to be co-expressed with IGF-II.
Objective: 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.
Methods: Sera from 145 cases of suspected NICTH, and postoperative sera from 25 surgical cases of confirmed NICTH were subjected to Western blot analysis and ELISA for IGF-II and quantitative PCR 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.
Results: 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 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 compared to their surgical margins.
Conclusion: Circulating miR-483-5p, derived from IGF-II-producing tumors, appears to be a more reliable biomarker for diagnosis and therapeutic outcome of NICTH compared to IGF-II or IGF-II to IGF-I ratio. These findings highlight the clinical utility of miR-483-5p in the management of NICTH.
Keywords: IGF-II; MicroRNA; Non-islet cell tumor hypoglycemia.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.