Plasma ceramides as a sexually dimorphic biomarker of pancreatic cancer-induced cachexia

BackgroundCancer patients who lose weight have low treatment tolerance and poor outcomes compared to cancer patients without weight loss, termed cachexia. Despite the clear increased risk for patients, diagnosing cachexia still primarily relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.MethodsTargeted metabolomics, including panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer. Receiver Operating Characteristic (ROC) analysis was undertaken to establish if any metabolite could effectively serve as a biomarker of cachexia.ResultsTargeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only elevated in cachectic males.ConclusionOur findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.Trial registrationNone.FundingSupport was provided through a pilot grant from U24DK100469 from the National Institute of Diabetes and Digestive and Kidney Diseases (The Mayo Clinic), National Cancer Institute P30CA016058 (The Ohio State University), National Cancer Institute R01CA180057 (DCG), American Cancer Society PF-15-156-01-CSM (EET), and a Weiss Postdoctoral Fellowship (EET).