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Imaging, Diagnosis, Prognosis

Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer

Joo Mi Yi, Angela A. Guzzetta, Vasudev Bailey, Stephanie R. Downing, Leander Van Neste, Katherine B Chiappinelli, Brian Keeley, Alejandro Stark, Alexander Herrera, Christopher L Wolfgang, Emmanouil P. Pappou, Christine A. Iacobuzio-Donahue, Michael Goggins, James G. Herman, Tza-Huei Wang, Stephen B. Baylin and Nita Ahuja
Joo Mi Yi
Research Institute, DIRAMS
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Angela A. Guzzetta
Dept. of Surgery, Johns Hopkins Medical Institutes
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Vasudev Bailey
Biomedical Engineering, Johns Hopkins School of Medicine
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Stephanie R. Downing
Department of Surgery, Howard University College of Medicine
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Leander Van Neste
Bioinformatics, MdxHealth
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Katherine B Chiappinelli
Oncology, The Johns Hopkins University, School of Medicine
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Brian Keeley
Biomedical Engineering, Johns Hopkins School of Medicine
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Alejandro Stark
Biomedical Engineering, Johns Hopkins School of Medicine
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Alexander Herrera
Surgery, Johns Hopkins School of Medicine
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Christopher L Wolfgang
Surgery, Johns Hopkins University
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Emmanouil P. Pappou
Dept. of Surgery, Johns Hopkins Medical Institutes
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Christine A. Iacobuzio-Donahue
Division of Gastrointestinal/Liver Pathology, The Johns Hopkins Hospital
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Michael Goggins
Department of Pathology, Medicine and Oncology, The Johns Hopkins Medical Institutions
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James G. Herman
Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Tza-Huei Wang
Biomedical Engineering, Johns Hopkins School of Medicine
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Stephen B. Baylin
Oncology, The Johns Hopkins University, SOM
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Nita Ahuja
Department of Medical Oncology, Johns Hopkins University School of Medicine
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  • For correspondence: nahuja1@jhmi.edu
DOI: 10.1158/1078-0432.CCR-12-3224
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Abstract

Purpose: Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer. Experimental Design: We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of 8 promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis including methylation and expression. We used a nanoparticle-enabled MOB (Methylation On Beads) technology to detect early stage pancreatic cancers by analyzing DNA methylation in patient serum. Results: We identified 2 novel genes, BNC1 (92%) and ADAMTS1, (68%) that showed a high frequency of methylation in pancreas cancers (n=143), up to 100% in PanIN-3 and 97% in Stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (n=42) from pancreas cancer patients, with a sensitivity for BNC1 of 79% (95%CI:66-91%) and for ADAMTS1 of 48% (95%CI:33-63%), while specificity was 89% for BNC1 (95%CI:76-100%) and 92% for ADAMTS1 (95%CI:82-100%). Overall sensitivity using both markers is 81% (95%CI:69-93%) and specificity is 85% (95%CI:71-99%). Conclusions: Promoter DNA methylation of BNC1 and ADAMTS1 are potential biomarkers to detect early stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early-detection of pancreatic cancer and has the potential to improve mortality from this disease.

  • Received October 15, 2012.
  • Revision received August 12, 2013.
  • Accepted September 15, 2013.
  • Copyright © 2013, American Association for Cancer Research.
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Published OnlineFirst October 2, 2013
doi: 10.1158/1078-0432.CCR-12-3224

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Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer
Joo Mi Yi, Angela A. Guzzetta, Vasudev Bailey, Stephanie R. Downing, Leander Van Neste, Katherine B Chiappinelli, Brian Keeley, Alejandro Stark, Alexander Herrera, Christopher L Wolfgang, Emmanouil P. Pappou, Christine A. Iacobuzio-Donahue, Michael Goggins, James G. Herman, Tza-Huei Wang, Stephen B. Baylin and Nita Ahuja
Clin Cancer Res October 2 2013 DOI: 10.1158/1078-0432.CCR-12-3224

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Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer
Joo Mi Yi, Angela A. Guzzetta, Vasudev Bailey, Stephanie R. Downing, Leander Van Neste, Katherine B Chiappinelli, Brian Keeley, Alejandro Stark, Alexander Herrera, Christopher L Wolfgang, Emmanouil P. Pappou, Christine A. Iacobuzio-Donahue, Michael Goggins, James G. Herman, Tza-Huei Wang, Stephen B. Baylin and Nita Ahuja
Clin Cancer Res October 2 2013 DOI: 10.1158/1078-0432.CCR-12-3224
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