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Metabonomic models of human pancreatic cancer using 1D proton NMR spectra of lipids in plasma

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Abstract

In this study, we hypothesized that the altered insulin and glucose levels in male pancreatic cancer patients reported in a recent JAMA article would result in an altered lipid profile in the blood of pancreatic cancer patients when compared to controls (Stolzenberg-Solomon et al., 2005). Proton nuclear magnetic resonance (NMR) spectra of human lipophilic plasma extracts were used in order to build partial least squares discriminant function (PLS-DF) models that classified samples as belonging to the pancreatic control group or to the pancreatic cancer group. The sensitivity, specificity, and overall accuracy of the PLS-DF models based on 4 bins were 96%, 88%, and 92%, respectively. The sensitivity, specificity, and overall accuracy of the PLS-DF models based on 5 bins were 98%, 94%, and 96%, respectively. The sensitivity, specificity and overall accuracy of both the 4-bin and 5-bin PLS-DF models dropped only 1–2% during leave-25%-out cross-validation testing. Mass spectrometric profiling of phospholipids in plasma found three phosphatidylinositols that were significantly lower in pancreatic cancer patients than in healthy controls. The cancer models are based upon changes in lipid profiles that may provide a more sensitive and accurate diagnosis of pancreatic cancer than current methods that are based upon a single biomarker.

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Abbreviations

NMR:

nuclear magnetic resonance

PLS-DF:

partial least squares discriminant function

LC-MS:

liquid chromatography-mass spectrometry

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Acknowledgment and disclaimer

Laura Schnackenberg was supported in part by appointments to ORAU Research Program at the National Center for Toxicological Research administered by the Oak Ridge Associated Universities through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. ACD/Labs 1D NMR manager is part of collaboration between NCTR and ACD/Labs. Waters MarkerLynx software is part of a “beta test” material transfer agreement between NCTR and Waters. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. The molecular epidemiological study conducted at M.D. Anderson Cancer Center is supported by NIH grant CA98380.

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Authors and Affiliations

  1. Division of Systems Toxicology, Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, 72079-9502, USA

    Richard D. Beger, Laura K. Schnackenberg, Ricky D. Holland & Yvonne Dragan

  2. MD Anderson Cancer Center, University of Texas, Houston, TX, 77030, USA

    Donghui Li

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  1. Richard D. Beger
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  2. Laura K. Schnackenberg
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  3. Ricky D. Holland
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  4. Donghui Li
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  5. Yvonne Dragan
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Correspondence to Richard D. Beger.

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Beger, R.D., Schnackenberg, L.K., Holland, R.D. et al. Metabonomic models of human pancreatic cancer using 1D proton NMR spectra of lipids in plasma. Metabolomics 2, 125–134 (2006). https://doi.org/10.1007/s11306-006-0026-2

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