纯胰液中 NPTX2 高甲基化可预测胰腺肿瘤。

NPTX2 hypermethylation in pure pancreatic juice predicts pancreatic neoplasms.

机构信息

Departments of Breast Surgery, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Am J Med Sci. 2013 Sep;346(3):175-80. doi: 10.1097/MAJ.0b013e31827b94b6.

DOI:10.1097/MAJ.0b013e31827b94b6

PMID:23360791

Abstract

The neuronal pentraxin II (NPTX2) gene is methylated in over 90% primary pancreatic cancer tissues but rarely in normal pancreatic ductal epithelia. Here, the authors investigated the utility of methylated NPTX2 as a diagnostic marker for pancreatic cancer in pure pancreatic juice samples of patients with benign and malignant pancreatic diseases, including pancreatic cancer, intraductal papillary mucinous neoplasm or chronic pancreatitis using methylation-specific polymerase chain reaction (MSP) and quantitative MSP. MSP assays revealed that the incidence of aberrant NPTX methylation in pure pancreatic juice samples was 64.5% (20 of 31) in patients with pancreatic cancer, 70.0% (7 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 33.3% (2 of 6) in patients with benign intraductal papillary mucinous neoplasm and 21.7% (5 of 23) in patients with chronic pancreatitis. NPTX2 hypermethylation in patients with chronic pancreatitis was significantly lower than that of pancreatic cancer (P < 0.01) or patients with intraductal papillary mucinous neoplasm (P < 0.05). At a cutoff value of 1.39 for quantitative MSP, the incidence of aberrant NPTX2 methylation was 61.3% (19 of 31) in patients with pancreatic cancer, 50.0% (5 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 0% in patients with benign intraductal papillary mucinous neoplasm and 8.7% (2 of 23) in patients with chronic pancreatitis. There was a significant difference in NPTX2 methylation between pancreatic cancer and chronic pancreatitis (P < 0.01). Our findings indicate that detection of aberrant methylation of NPTX2 in pure pancreatic juice samples could be useful as a molecular marker to discriminate between patients with malignant and benign disease of the pancreas.

摘要

神经元五联蛋白 II (NPTX2) 基因在超过 90%的原发性胰腺癌组织中发生甲基化，但在正常胰腺导管上皮中很少发生。作者在这里使用甲基化特异性聚合酶链反应 (MSP) 和定量 MSP 检测了纯胰腺液样本中甲基化 NPTX2 作为胰腺良恶性疾病（包括胰腺癌、导管内乳头状黏液性肿瘤或慢性胰腺炎）患者的诊断标志物的应用价值。MSP 检测显示，在胰腺癌患者的纯胰腺液样本中，异常 NPTX 甲基化的发生率为 64.5%（31 例中有 20 例），恶性导管内乳头状黏液性肿瘤患者为 70.0%（10 例中有 7 例），良性导管内乳头状黏液性肿瘤患者为 33.3%（6 例中有 2 例），慢性胰腺炎患者为 21.7%（23 例中有 5 例）。与慢性胰腺炎患者相比，NPTX2 高甲基化在胰腺癌患者中显著更高（P<0.01）或在导管内乳头状黏液性肿瘤患者中更高（P<0.05）。在定量 MSP 的截断值为 1.39 时，胰腺癌患者中异常 NPTX2 甲基化的发生率为 61.3%（31 例中有 19 例），恶性导管内乳头状黏液性肿瘤患者为 50.0%（10 例中有 5 例），良性导管内乳头状黏液性肿瘤患者为 0%，慢性胰腺炎患者为 8.7%（23 例中有 2 例）。在胰腺癌和慢性胰腺炎之间，NPTX2 甲基化存在显著差异（P<0.01）。我们的研究结果表明，检测纯胰腺液样本中 NPTX2 的异常甲基化可能有助于作为一种分子标志物来区分胰腺的良恶性疾病。