Novel methylation biomarker panel for the early detection of pancreatic cancer

Joo Mi Yi, Angela A. Guzzetta, Vasudev J. Bailey, Stephanie R. Downing, Leander Van Neste, Katherine B. Chiappinelli, Brian P. Keeley, Alejandro Stark, Alexander Herrera, Christopher Wolfgang, Emmanouil P. Pappou, Christine A. Iacobuzio-Donahue, Michael G. Goggins, James G. Herman, Tza Huei Wang, Stephen B. Baylin, Nita Ahuja

Research output: Contribution to journalArticle

Abstract

Purpose: Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modalityfor the earlydetectionofthis disease. Here, weidentify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as apromising biomarker detection strategy meriting investigation in pancreatic cancer. Experimental Design:Weusedagenome-wide pharmacologic transcriptome approach toidentify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of eight promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis, including methylation and expression. We used a nanoparticle-enabled methylation on beads (MOB) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum. Results: We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreatic 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 patients with pancreatic cancer, with a sensitivity for BNC1 of 79% [95% confidence interval (CI), 66%-91%] and for ADAMTS1 of 48% (95% CI, 33%-63%), whereas specificity was 89% for BNC1 (95%CI, 76%-100%) and 92% for ADAMTS1(95%CI, 82%-100%).Overallsensitivity 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 is a potential biomarker 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.

Original languageEnglish (US)
Pages (from-to)6544-6555
Number of pages12
JournalClinical Cancer Research
Volume19
Issue number23
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yi, J. M., Guzzetta, A. A., Bailey, V. J., Downing, S. R., Neste, L. V., Chiappinelli, K. B., Keeley, B. P., Stark, A., Herrera, A., Wolfgang, C., Pappou, E. P., Iacobuzio-Donahue, C. A., Goggins, M. G., Herman, J. G., Wang, T. H., Baylin, S. B., & Ahuja, N. (2013). Novel methylation biomarker panel for the early detection of pancreatic cancer. Clinical Cancer Research, 19(23), 6544-6555. https://doi.org/10.1158/1078-0432.CCR-12-3224