Insulin-like peptide 3 (INSL3) is not a biomarker for pancreatic ductal adenocarcinoma

Ravinder Anand-Ivell¹Xinyuan Yang¹Ruediger Braun²Hendrik Ungefroren³Richard Ivell^4*

• ¹School of Biosciences, University of Nottingham, Sutton Bonington, United Kingdom
• ²Department of Surgery, University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck,, Luebeck, Germany
• ³First Department of Medicine, University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck, Luebeck, Germany
• ⁴University of Nottingham, Nottingham, United Kingdom

Pancreatic ductal carcinoma (PDAC) is a rapid-growing cancer with very poor prognosis. It is therefore important to develop novel specific biomarkers to identify such cancers as early as possible. In a recent article published in Nature Cell Biology, Yeom and colleagues postulated that circulating insulin-like peptide 3 (INSL3) might serve as such a biomarker. Experiments were first conducted in Drosophila to show that the Dilp8/Lgr3 system regulated the fly equivalent of cachexia. This was then translated to the human to imply the involvement of the INSL3/RXFP2 system in PDAC-associated cachexia and that circulating INSL3 might serve as an early PDAC biomarker. We have now analysed blood and tumor tissue from PDAC patients using a well-validated and recognized INSL3 immunoassay and specific anti-human INSL3 antibodies and find no evidence to support these claims. We consider that this is largely due to Yeom and colleagues using a poorly validated immunoassay and antibodies for INSL3. Unfortunately, therefore this peptide is not suitable to be considered as a PDAC biomarker.