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WIF-1启动子区域高甲基化作为非小细胞肺癌相关恶性胸腔积液的辅助诊断标志物

WIF-1 promoter region hypermethylation as an adjuvant diagnostic marker for non-small cell lung cancer-related malignant pleural effusions.

作者信息

Yang Tsung-Ming, Leu Shaw-Wei, Li Jhy-Ming, Hung Ming-Szu, Lin Chu-Huan, Lin Yu-Ching, Huang Tung-Jung, Tsai Ying-Huang, Yang Cheng-Ta

机构信息

Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, 6 West Chiapu Road, Putzu, Chiayi, 613, Taiwan.

出版信息

J Cancer Res Clin Oncol. 2009 Jul;135(7):919-24. doi: 10.1007/s00432-008-0527-7. Epub 2008 Dec 16.

Abstract

PURPOSE

Malignant pleural effusion is an important staging criterion in non-small cell lung cancer (NSCLC). Although cytologic examination remains the major diagnostic tool for NSCLC-related malignant pleural effusion, sometimes other invasive methods maybe required. Aberrant activation of Wnt signaling pathway due to Wnt inhibitory factor-1 (WIF-1) promoter region hypermethylation is common in NSCLC, and can be specifically detected by methylation-specific polymerase chain reaction (MSP). We hypothesized that WIF-1 promoter region MSP can be used to improve the diagnostic yield of NSCLC-related malignant pleural effusion.

METHODS

We performed WIF-1 promoter region MSP in 36 definite malignant pleural effusions from consecutive NSCLC patients and 35 pleural effusion specimens of benign origin. Pleural effusion cells were collected for DNA extraction. After bisulfite treatment, DNA was amplified by methylation-specific and unmethylation-specific primers, respectively, to identify the methylation status of WIF-1 promoter region.

RESULTS

The results of WIF-1 promoter region MSP were positive in 25 (69.4%) of 36 NSCLC patients with malignant pleural effusion. In addition, the results of WIF-1 promoter region MSP were negative in all 35 patients with pleural effusion of benign origin. The age, gender, and smoking status of patients were not correlated with the methylation status of WIF-1 promoter region in NSCLC-related malignant pleural effusion.

CONCLUSIONS

WIF-1 promoter region MSP might be used as an adjuvant tool to complement cytologic examination for the diagnosis of NSCLC-related malignant pleural effusion.

摘要

目的

恶性胸腔积液是非小细胞肺癌(NSCLC)的一项重要分期标准。尽管细胞学检查仍是NSCLC相关恶性胸腔积液的主要诊断工具,但有时可能需要其他侵入性方法。Wnt抑制因子-1(WIF-1)启动子区域高甲基化导致的Wnt信号通路异常激活在NSCLC中很常见,并且可以通过甲基化特异性聚合酶链反应(MSP)进行特异性检测。我们假设WIF-1启动子区域MSP可用于提高NSCLC相关恶性胸腔积液的诊断率。

方法

我们对36例连续NSCLC患者的确诊恶性胸腔积液和35例良性胸腔积液标本进行了WIF-1启动子区域MSP。收集胸腔积液细胞用于DNA提取。亚硫酸氢盐处理后,分别用甲基化特异性引物和非甲基化特异性引物对DNA进行扩增,以确定WIF-1启动子区域的甲基化状态。

结果

36例NSCLC合并恶性胸腔积液患者中,25例(69.4%)WIF-1启动子区域MSP结果为阳性。此外,35例良性胸腔积液患者的WIF-1启动子区域MSP结果均为阴性。NSCLC相关恶性胸腔积液患者的年龄、性别和吸烟状况与WIF-1启动子区域的甲基化状态无关。

结论

WIF-1启动子区域MSP可作为辅助工具,补充细胞学检查用于诊断NSCLC相关恶性胸腔积液。

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