title: Distinguishing Benign from Malignant Pancreatic and Periampullary Lesions Using Combined Use of ¹H-NMR Spectroscopy and Gas Chromatography-Mass Spectrometry.
abstract: Previous work demonstrated that serum metabolomics can distinguish pancreatic cancer from benign disease. However, in the clinic, non-pancreatic periampullary cancers are difficult to distinguish from pancreatic cancer. Therefore, to test the clinical utility of this technology, we determined whetheranypancreatic and periampullary adenocarcinoma could be distinguished from benign masses and biliary strictures. Sera from 157 patients with malignant and benign pancreatic and periampullary lesions were analyzed using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). Multivariate projection modeling using SIMCA-P+ software in training datasets (n= 80) was used to generate the best models to differentiate disease states. Models were validated in test datasets (n= 77). The final ¹H-NMR spectroscopy and GC-MS metabolomic profiles consisted of 14 and 18 compounds, with AUROC values of 0.74 (SE 0.06) and 0.62 (SE 0.08), respectively. The combination of ¹H-NMR spectroscopy and GC-MS metabolites did not substantially improve this performance (AUROC 0.66, SE 0.08). In patients with adenocarcinoma, glutamate levels were consistently higher, while glutamine and alanine levels were consistently lower. Pancreatic and periampullary adenocarcinomas can be distinguished from benign lesions. To further enhance the discriminatory power of metabolomics in this setting, it will be important to identify the metabolomic changes that characterize each of the subclasses of this heterogeneous group of cancers.
authors.affiliation: Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada. yarrow.mcconnell@gmail.com.|Department of Surgery, University of Calgary, Calgary, AB T2N 4N2, Canada. yarrow.mcconnell@gmail.com.
authors.forename: Yarrow J
authors.initials: YJ
authors.lastname: McConnell
authors.affiliation: Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada. farshidf@ucalgary.ca.
authors.forename: Farshad
authors.initials: F
authors.lastname: Farshidfar
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, AB T2N 4N2, Canada. aalim@upenn.edu.|Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA. aalim@upenn.edu.
authors.forename: Aalim M
authors.initials: AM
authors.lastname: Weljie
authors.affiliation: Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada. karen.kopciuk@albertahealthservices.ca.|Department of Mathematics and Statistics, University of Calgary, Calgary, AB T2N 4N2, Canada. karen.kopciuk@albertahealthservices.ca.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kopciuk
authors.affiliation: Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada. elijah.dixon@albertahealthservices.ca.|Department of Surgery, University of Calgary, Calgary, AB T2N 4N2, Canada. elijah.dixon@albertahealthservices.ca.
authors.forename: Elijah
authors.initials: E
authors.lastname: Dixon
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB T2N 4N2, Canada. ball.chad@gmail.com.
authors.forename: Chad G
authors.initials: CG
authors.lastname: Ball
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB T2N 4N2, Canada. francis.sutherland@albertahealthservices.ca.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Sutherland
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, AB T2N 4N2, Canada. vogel@ucalgary.ca.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
authors.affiliation: Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada. bathe@ucalgary.ca.|Department of Surgery, University of Calgary, Calgary, AB T2N 4N2, Canada. bathe@ucalgary.ca.
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Bathe
keywords: biomarkers; metabolomics; pancreatic cancer; periampullary adenocarcinoma