Metabolic system alterations in pancreatic cancer patient serum: Potential for early detection

The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality.

Ritchie et al BMC Cancer 2013, 13:416 http://www.biomedcentral.com/1471-2407/13/416 RESEARCH ARTICLE Open Access Metabolic system alterations in pancreatic cancer patient serum: potential for early detection Shawn A Ritchie1*†, Hirofumi Akita2†, Ichiro Takemasa2*, Hidetoshi Eguchi2, Elodie Pastural1,3, Hiroaki Nagano2, Morito Monden2, Yuichiro Doki2, Masaki Mori2, Wei Jin1, Tolulope T Sajobi1,4, Dushmanthi Jayasinghe1, Bassirou Chitou1, Yasuyo Yamazaki1, Thayer White5 and Dayan B Goodenowe1 Abstract Background: The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects Methods: A non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50) Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasims (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population Results: FI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p