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Cancer Prevention Research
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Research Article

THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement

Shirsa Udgata, Naomi Takenaka, William R. Bamlet, Ann L. Oberg, Stephanie S. Yee, Erica L. Carpenter, Daniel Herman, Jungsun Kim, Gloria M. Petersen and Kenneth S. Zaret
Shirsa Udgata
1Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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  • ORCID record for Shirsa Udgata
Naomi Takenaka
1Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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William R. Bamlet
2Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
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Ann L. Oberg
2Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
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  • ORCID record for Ann L. Oberg
Stephanie S. Yee
3Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Erica L. Carpenter
3Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Daniel Herman
4Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Jungsun Kim
1Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Gloria M. Petersen
5Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
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Kenneth S. Zaret
1Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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  • For correspondence: zaret@upenn.edu
DOI: 10.1158/1940-6207.CAPR-20-0403
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed too late for effective therapy. The classic strategy for early detection biomarker advancement consists of initial retrospective phases of discovery and validation with tissue samples taken from individuals diagnosed with disease, compared with controls. Using this approach, we previously reported the discovery of a blood biomarker panel consisting of thrombospondin-2 (THBS2) and CA19-9 that together could discriminate resectable stage I and IIa PDAC as well as stages III and IV PDAC, with c-statistic values in the range of 0.96 to 0.97 in two phase II studies. We now report that in two studies of blood samples prospectively collected from 1 to 15 years prior to a PDAC diagnosis (Mayo Clinic and PLCO cohorts), THBS2 and/or CA19-9 failed to discriminate cases from healthy controls at the AUC = 0.8 needed. We conclude that PDAC progression may be heterogeneous and for some individuals can be more rapid than generally appreciated. It is important that PDAC early-detection studies incorporate high-risk, prospective prediagnostic cohorts into discovery and validation studies.

Prevention Relevance: A blood biomarker panel of THBS2 and CA19-9 detects early stages of pancreatic ductal adenocarcinoma at diagnosis, but not when tested across a population up to 1 year earlier. Our findings suggest serial sampling over time, using prospectively collected samples for biomarker discovery, and more frequent screening of high-risk individuals.

Footnotes

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

  • Synopsis: The contrast of a successful biomarker panel on blood sampled at the time of diagnosis of pancreatic cancer, but not on blood sampled prediagnostically, indicates that renewed attention to design and construction of biospecimen sets is critical to advance early detection.

  • Cancer Prev Res 2020;XX:XX–XX

  • Received July 30, 2020.
  • Revision received September 25, 2020.
  • Accepted October 7, 2020.
  • ©2020 American Association for Cancer Research.

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This OnlineFirst version was published on December 4, 2020
doi: 10.1158/1940-6207.CAPR-20-0403

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THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement
Shirsa Udgata, Naomi Takenaka, William R. Bamlet, Ann L. Oberg, Stephanie S. Yee, Erica L. Carpenter, Daniel Herman, Jungsun Kim, Gloria M. Petersen and Kenneth S. Zaret
Cancer Prev Res December 4 2020 DOI: 10.1158/1940-6207.CAPR-20-0403

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THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement
Shirsa Udgata, Naomi Takenaka, William R. Bamlet, Ann L. Oberg, Stephanie S. Yee, Erica L. Carpenter, Daniel Herman, Jungsun Kim, Gloria M. Petersen and Kenneth S. Zaret
Cancer Prev Res December 4 2020 DOI: 10.1158/1940-6207.CAPR-20-0403
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eISSN: 1940-6215
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