Abstract
Early detection of pancreatic ductal carcinoma (PDAC) is critically important because by the time PDAC is detected almost 80% of patients are surgically unresectable1. While imaging with CT, MRI and ultrasound is making significant inroads in PDAC detection, the costs associated with imaging impose a barrier for routine screening. Plasma based detection of PDAC would provide a relatively inexpensive and easy method for routine screening for the purpose of early detection. Metabolic profiling of plasma samples using high resolution 1H MRS provides an opportunity to assist in the detection of PDAC. Here we characterized the plasma metabolome of normal subjects, subjects with benign pancreatic disease, and subjects with PDAC to evaluate the ability of 1H MRS to identify metabolic changes in plasma associated with PDAC.
Plasma from patients with PDAC (n=4), patients with benign pancreatic disease (n=2) and from healthy control subjects (n=4) were included in this study. Final diagnosis was established by histopathological evaluation of surgical specimens. Three hundred micro liter of D2O phosphate buffer saline (NaCl 0.9% in 90% D2O) was mixed with 300 μL of plasma and transferred to 5 mm NMR tubes. High-resolution 1H MRS was performed on an Avance 750 MHz Bruker MR spectrometer. The Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence with water suppression [PRESET-90°-(d-180-d)n-Aq] was performed to remove short T2 components arising due to the presence of macromolecules2.
The metabolites were identified and quantified from 1H MRS spectra from the three groups. Even with a small sample size clear differences were identified in metabolites such as lactate, pyruvate, β-hydroxybutyrate, acetate and acetoacetate in plasma from PDAC subjects compared to normal subjects. The increase of lactate and pyruvate detected in plasma may reflect altered glucose metabolism occurring in PDAC. β-hydroxybutyrate, acetate and acetoacetate are involved in ketone body synthesis and may reflect altered ketone body metabolism occurring in PDAC.
In a recent study, higher levels of ketone bodies and lactate were detected in the serum of rats with 7,12-dimethylben(a)anthracen (DMBA)-induced pancreatic intraepithelial neoplasia (PanIN) compared to plasma. Interestingly, with progression to PDAC several of these metabolites decreased3. Our data support further investigation of 1H MRS of human plasma to detect PDAC in combination with techniques such as circulating tumor cell phenotyping
References:
(1) Kotteas, E., et al. J Cancer Res Clin Oncol 2016, 142, 1795-1805.
(2) Van, Q. N., et al. Biochem Biophys Res Commun 2003, 301, 952-959.
(3) Lin, X., et al. Mol Biosyst 2016, 12, 2883-2892.
This work was supported by NIH R01 CA193365.
Citation Format: Santosh K. Bharti, Michael Goggins, Zaver M. Bhujwalla. High-resolution 1H <MRS> human plasma profiling of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2509. doi:10.1158/1538-7445.AM2017-2509
- ©2017 American Association for Cancer Research.
Volume 77, Issue 13 Supplement
