TY - JOUR
T1 - Novel methylation biomarker panel for the early detection of pancreatic cancer
AU - Yi, Joo Mi
AU - Guzzetta, Angela A.
AU - Bailey, Vasudev J.
AU - Downing, Stephanie R.
AU - Neste, Leander Van
AU - Chiappinelli, Katherine B.
AU - Keeley, Brian P.
AU - Stark, Alejandro
AU - Herrera, Alexander
AU - Wolfgang, Christopher
AU - Pappou, Emmanouil P.
AU - Iacobuzio-Donahue, Christine A.
AU - Goggins, Michael G.
AU - Herman, James G.
AU - Wang, Tza Huei
AU - Baylin, Stephen B.
AU - Ahuja, Nita
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84890276015&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-12-3224
DO - 10.1158/1078-0432.CCR-12-3224
M3 - Article
C2 - 24088737
AN - SCOPUS:84890276015
SN - 1078-0432
VL - 19
SP - 6544
EP - 6555
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -