Supplementary Material for: CA19-9 in Combination with Methylated HOXA1 and SST Is Useful to Diagnose Stage I Pancreatic Cancer

Introduction: 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. Methods: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) 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. Results: 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 mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. Conclusion: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.

引言：本团队此前开发了一种新型甲基化检测技术——联合限制性内切酶数字PCR（combined restriction digital PCR, CORD）检测法，该方法通过甲基化敏感限制性内切酶处理DNA并结合液滴式数字PCR（droplet digital PCR）完成检测。
方法：本研究采用CORD检测法联合糖类抗原19-9（CA19-9），评估血清中甲基化同源盒A1（methylated Homeobox A1, mHOXA1）与甲基化生长抑素（methylated somatostatin, mSST）对胰腺癌的诊断效能。本次研究共纳入82名健康个体、13例胰腺良性疾病患者、3例分支型导管内乳头状黏液瘤（intraductal papillary mucinous neoplasm, IPMN）患者以及91例胰腺癌患者的血清样本。
结果：单项标志物检测中，CA19-9对各分期胰腺癌、I期胰腺癌的敏感度及特异度分别为71.4%、50.0%、94.9%；mHOXA1对应三项指标分别为51.6%、68.8%、90.8%；mSST对应三项指标分别为50.1%、68.8%、94.9%。联合标志物检测中，mHOXA1联合CA19-9的三项指标分别为86.8%、81.3%、85.7%；mSST联合CA19-9的三项指标分别为86.8%、87.5%、89.8%；三项标志物联合检测的三项指标分别为89.0%、87.5%、85.7%。
结论：将mHOXA1、mSST与CA19-9联合检测，可有效检出胰腺癌，甚至可用于早期胰腺癌的诊断。