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Imaging, Diagnosis, Prognosis

Serum Biomarker Panels for the Detection of Pancreatic Cancer

Randall E. Brand, Brian M. Nolen, Herbert J. Zeh, Peter J. Allen, Mohamad A. Eloubeidi, Michael Goldberg, Eric Elton, Juan P. Arnoletti, John D. Christein, Selwyn M. Vickers, Christopher J. Langmead, Douglas P. Landsittel, David C. Whitcomb, William E. Grizzle and Anna E. Lokshin
Randall E. Brand
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Brian M. Nolen
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Herbert J. Zeh
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Peter J. Allen
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Mohamad A. Eloubeidi
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Michael Goldberg
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Eric Elton
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Juan P. Arnoletti
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John D. Christein
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Selwyn M. Vickers
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Christopher J. Langmead
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Douglas P. Landsittel
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David C. Whitcomb
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William E. Grizzle
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Anna E. Lokshin
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DOI: 10.1158/1078-0432.CCR-10-0248 Published February 2011
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Abstract

Purpose: Serum–biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations.

Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers.

Results: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19–9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19–9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19–9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19–9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19–9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer.

Conclusions: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations. Clin Cancer Res; 17(4); 805–16. ©2010 AACR.

See commentary p. 635

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Received January 28, 2010.
  • Revision received October 25, 2010.
  • Accepted November 7, 2010.
  • ©2011 American Association for Cancer Research.
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Clinical Cancer Research: 17 (4)
February 2011
Volume 17, Issue 4
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Serum Biomarker Panels for the Detection of Pancreatic Cancer
Randall E. Brand, Brian M. Nolen, Herbert J. Zeh, Peter J. Allen, Mohamad A. Eloubeidi, Michael Goldberg, Eric Elton, Juan P. Arnoletti, John D. Christein, Selwyn M. Vickers, Christopher J. Langmead, Douglas P. Landsittel, David C. Whitcomb, William E. Grizzle and Anna E. Lokshin
Clin Cancer Res February 15 2011 (17) (4) 805-816; DOI: 10.1158/1078-0432.CCR-10-0248

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Serum Biomarker Panels for the Detection of Pancreatic Cancer
Randall E. Brand, Brian M. Nolen, Herbert J. Zeh, Peter J. Allen, Mohamad A. Eloubeidi, Michael Goldberg, Eric Elton, Juan P. Arnoletti, John D. Christein, Selwyn M. Vickers, Christopher J. Langmead, Douglas P. Landsittel, David C. Whitcomb, William E. Grizzle and Anna E. Lokshin
Clin Cancer Res February 15 2011 (17) (4) 805-816; DOI: 10.1158/1078-0432.CCR-10-0248
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