CA19-9 in Combination with Methylated <b><i>HOXA1</i></b> and <b><i>SST</i></b> Is Useful to Diagnose Stage I Pancreatic Cancer

Abstract

<b><i>Introduction:</i></b> We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. <b><i>Methods:</i></b> In this study, we assessed the diagnostic performance of serum methylated <i>Homeobox A1</i> (m<i>HOXA1</i>) and methylated <i>somatostatin</i> (m<i>SST</i>) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. <b><i>Results:</i></b> For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for m<i>HOXA1</i>; and 50.1%, 68.8%, and 94.9% for m<i>SST</i>. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined m<i>HOXA1</i> and CA19-9; 86.8%, 87.5%, and 89.8% for combined m<i>SST</i> and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. <b><i>Conclusion:</i></b> The combination of m<i>HOXA1</i> and m<i>SST</i> with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.