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

Pancreatic ductal carcinoma (PDAC) is a rapidly growing cancer with a 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 humans 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 analyzed blood and tumor tissue from PDAC patients using a well-validated and recognized INSL3 immunoassay and specific antihuman 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 for consideration as a PDAC biomarker.