CA19-9 与血液游离甲基化 RUNX3 联合检测可能有助于诊断Ⅰ期胰腺癌。

Combination of CA19-9 and Blood Free-Circulating Methylated RUNX3 May Be Useful to Diagnose Stage I Pancreatic Cancer.

机构信息

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan,

出版信息

Oncology. 2021;99(4):234-239. doi: 10.1159/000511940. Epub 2021 Jan 13.

DOI:10.1159/000511940

PMID:33440396

Abstract

BACKGROUND

Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (RUNX3) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment.

OBJECTIVES

We evaluated the sensitivity and specificity of serum DNA testing of methylated RUNX3 by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals.

RESULTS

The CORD assay of methylated RUNX3 had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated RUNX3 and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer.

CONCLUSIONS

ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.

摘要

背景

尽管血清碳水化合物抗原 19-9（CA19-9）被广泛用作监测治疗反应的胰腺癌有用的生物标志物，但由于其对小肿瘤的敏感性有限，因此不建议用于早期胰腺癌的筛查。因此，发现新的血清生物标志物来补充 CA19-9 以提高敏感性至关重要。虽然甲基化 runt 相关转录因子 3（RUNX3）是胰腺癌的生物标志物，但从少量血清样本中通过常规亚硫酸氢盐基甲基化测定进行检测非常困难。因此，我们开发了一种新的甲基化测定方法，即联合限制性数字 PCR（CORD）测定法，该方法无需 DNA 亚硫酸氢盐处理即可在小 DNA 样本量中甚至对一个甲基化基因的拷贝进行计数。

目的

我们评估了 CORD 测定法联合和不联合 CA19-9 检测甲基化 RUNX3 血清 DNA 在 55 例胰腺癌患者、12 例良性胰腺疾病患者和 80 例健康个体中的敏感性和特异性。

结果

CORD 测定法检测甲基化 RUNX3 的敏感性为 50.9%（28/55），特异性为 93.5%（86/92）。CORD 测定法联合甲基化 RUNX3 和 CA19-9 的组合对所有阶段的胰腺癌的敏感性为 85.5%（47/55），特异性为 93.5%（86/92），对 I 期胰腺癌的敏感性为 77.8%（7/9）。