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Pancreatic Ductal Adenocarcinoma is Associated with a Distinct Urinary Metabolomic Signature

  • Translational Research and Biomarkers
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ABSTRACT

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis in part due to the lack of early detection and screening methods. Metabolomics provides a means for noninvasive screening of tumor-associated perturbations in cellular metabolism.

Methods

Urine samples of PDAC patients (n = 32), healthy age and gender-matched controls (n = 32), and patients with benign pancreatic conditions (n = 25) were examined using 1H-NMR spectroscopy. Targeted profiling of spectra permitted quantification of 66 metabolites. Unsupervised (principal component analysis, PCA) and supervised (orthogonal partial-least squares discriminant analysis, OPLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra using SIMCA-P+ (version 12, Umetrics, Sweden).

Results

Clear distinction between PDAC and controls was noted when using OPLS-DA. Significant differences in metabolite concentrations between cancers and controls (p < 0.001) were noted. Model parameters for both goodness of fit, and predictive capability were high (R 2 = 0.85; Q 2 = 0.59, respectively). Internal validation methods were used to confirm model validity. Sensitivity and specificity of the multivariate OPLS-DA model were summarized using a receiver operating characteristics (ROC) curve, with an area under the curve (AUROC) = 0.988, indicating strong predictive power. Preliminary analysis revealed an AUROC = 0.958 for the model of benign pancreatic disease compared with PDAC, and suggest that the cancer-associated metabolomic signature dissipates following RO resection.

Conclusions

Urinary metabolomics detected distinct differences in the metabolic profiles of pancreatic cancer compared with healthy controls and benign pancreatic disease. These preliminary results suggest that metabolomic approaches may facilitate discovery of novel pancreatic cancer biomarkers.

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ACKNOWLEDGMENT

The authors thank Mrs. Barb Prodor and the Alberta Cancer Foundation as well as the Canadian Association of General Surgeons for their financial support.

CONFLICT OF INTEREST

There are no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Surgery, 2D2.01 Walter Mackenzie Health Sciences Center, University of Alberta, Edmonton, AB, Canada

    Vanessa W. Davis BSc, MD & Daniel E. Schiller MSc, MD

  2. School of Public Health, University of Alberta, Edmonton, AB, Canada

    Dean Eurich BSP, PhD

  3. Department of Surgery and Oncology, University of Calgary, Calgary, AB, Canada

    Oliver F. Bathe MSc, MD

  4. Cross Cancer Institute, Edmonton, AB, Canada

    Michael B. Sawyer BSc, MD

Authors
  1. Vanessa W. Davis BSc, MD
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  2. Daniel E. Schiller MSc, MD
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Correspondence to Vanessa W. Davis BSc, MD.

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Davis, V.W., Schiller, D.E., Eurich, D. et al. Pancreatic Ductal Adenocarcinoma is Associated with a Distinct Urinary Metabolomic Signature. Ann Surg Oncol 20 (Suppl 3), 415–423 (2013). https://doi.org/10.1245/s10434-012-2686-7

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  • DOI: https://doi.org/10.1245/s10434-012-2686-7

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