Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, People's Republic of China.
Med Oncol. 2011 Dec;28 Suppl 1:S175-84. doi: 10.1007/s12032-010-9683-0. Epub 2010 Oct 5.
The MUC4 gene could have a key role in the progression of pancreatic cancer, but the quantitative measurement of its expression in clinical tissue samples remains a challenge. The correlations between MUC4 promoter methylation status in vivo and either pancreatic cancer progression or MUC4 mRNA expression need to be demonstrated. We used the techniques of quantitative real-time PCR and DNA methylation-specific PCR combined microdissection to precisely detect MUC4 expression and promoter methylation status in 116 microdissected foci from 57 patients with pancreatic ductal adenocarcinoma. Both mRNA expression and hypomethylation frequency increased from normal to precancerous lesions to pancreatic cancer. Multivariate Cox regression analysis showed that high-level MUC4 expression (P = 0.008) and tumor-node-metastasis staging (P = 0.038) were significant independent risk factors for predicting the prognosis of 57 patients. The MUC4 mRNA expression was not significantly correlated with promoter methylation status in 30 foci of pancreatic ductal adenocarcinoma. These results suggest that high mRNA expression and hypomethylation of the MUC4 gene could be involved in carcinogenesis and in the malignant development of pancreatic ductal adenocarcinoma. The MUC4 mRNA expression may become a new prognostic marker for pancreatic cancer. Microdissection-based quantitative real-time PCR and methylation-specific PCR contribute to the quantitative detection of MUC4 expression in clinical samples and reflect the epigenetic regulatory mechanisms of MUC4 in vivo.
MUC4 基因可能在胰腺癌的进展中起关键作用，但在临床组织样本中定量测量其表达仍然是一个挑战。需要证明 MUC4 启动子甲基化状态与体内胰腺癌进展或 MUC4 mRNA 表达之间的相关性。我们使用定量实时 PCR 和 DNA 甲基化特异性 PCR 联合显微切割技术，精确检测了 57 例胰腺导管腺癌中 116 个微切割焦点的 MUC4 表达和启动子甲基化状态。mRNA 表达和低甲基化频率从正常到癌前病变再到胰腺癌逐渐增加。多变量 Cox 回归分析显示，高水平的 MUC4 表达（P=0.008）和肿瘤-淋巴结-转移分期（P=0.038）是预测 57 例患者预后的显著独立危险因素。在 30 个胰腺导管腺癌焦点中，MUC4 mRNA 表达与启动子甲基化状态无显著相关性。这些结果表明，MUC4 基因的高 mRNA 表达和低甲基化可能参与了胰腺癌的发生和胰腺导管腺癌的恶性发展。MUC4 mRNA 表达可能成为胰腺癌的新预后标志物。基于显微切割的定量实时 PCR 和甲基化特异性 PCR 有助于对临床样本中 MUC4 表达进行定量检测，并反映了 MUC4 在体内的表观遗传调控机制。
