CDH1在肺癌中的临床病理意义及潜在药物靶点：一项荟萃分析与文献综述
Clinicopathological significance and potential drug targeting of CDH1 in lung cancer: a meta-analysis and literature review.
作者信息
Yu Qiaowen, Guo Qisen, Chen Liangan, Liu Shuwei
机构信息
Shandong Provincial Key Laboratory of Mental Disorders, Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Beijing, People's Republic of China.
Respiratory Medicine, Shandong Cancer Hospital, Jinan, Beijing, People's Republic of China.
出版信息
Drug Des Devel Ther. 2015 Apr 15;9:2171-8. doi: 10.2147/DDDT.S78537. eCollection 2015.
BACKGROUND
CDH1 is a protein encoded by the CDH1 gene in humans. Mutations in this gene are linked with several types of cancer. Loss of CDH1 function contributes to the progression of cancer by increasing proliferation, invasion, and/or metastasis. However, the association between and clinicopathological significance of CDH1 promoter methylation and lung cancer remains unclear. In this study, we systematically reviewed the studies of CDH1 promoter methylation and lung cancer, and evaluated the association between CDH1 promoter methylation and lung cancer using meta-analysis methods.
METHODS
A comprehensive search of the PubMed and Embase databases was performed up to July 2014. The methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analyses of pooled data were performed. Odds ratios (ORs) were calculated and summarized.
RESULTS
Finally, an analysis of 866 patients with non-small cell lung cancer from 13 eligible studies was performed. The CDH1 methylation level in the cancer group was significantly higher than in the controls (OR 3.89, 95% confidence interval [CI] 2.87-5.27, P<0.00001). However, there were no correlations between CDH1 promoter methylation and clinicopathological characteristics (sex status, OR 0.78, 95% CI 0.41-1.50, P=0.46; smoking history, OR 0.97, 95% CI 0.53-1.79, P=0.93; pathological type, OR 0.97, 95% CI 0.59-1.60, P=0.91; clinical staging, OR 1.48, 95% CI 0.81-2.68, P=0.2; lymph node metastasis, OR 0.68, 95% CI 0.13-3.63, P=0.65; or differentiation degree, OR 1.01, 95% CI 0.34-3.02, P=0.99).
CONCLUSION
The results of this meta-analysis suggest that CDH1 methylation is associated with an increased risk of lung cancer. CDH1 hypermethylation, which induces inactivation of the CDH1 gene, plays an important role in carcinogenesis and may serve as a potential drug target in lung cancer. However, CDH1 methylation does not correlate with other factors, such as smoking history, clinical stage, pathological type, sex status, lymph node metastasis, or degree of differentiation.
背景
CDH1是人类CDH1基因编码的一种蛋白质。该基因的突变与多种类型的癌症相关。CDH1功能丧失通过增加增殖、侵袭和/或转移促进癌症进展。然而，CDH1启动子甲基化与肺癌之间的关联及其临床病理意义仍不清楚。在本研究中，我们系统回顾了CDH1启动子甲基化与肺癌的研究，并使用荟萃分析方法评估了CDH1启动子甲基化与肺癌之间的关联。
方法
截至2014年7月，对PubMed和Embase数据库进行了全面检索。还评估了研究的方法学质量。数据由两名审阅者独立提取和评估。对汇总数据进行分析。计算并汇总比值比（OR）。
结果
最后，对13项符合条件的研究中的866例非小细胞肺癌患者进行了分析。癌症组的CDH1甲基化水平显著高于对照组（OR 3.89，95%置信区间[CI] 2.87 - 5.27，P < 0.00001）。然而，CDH1启动子甲基化与临床病理特征之间无相关性（性别状态，OR 0.78，95% CI 0.41 - 1.50，P = 0.46；吸烟史，OR 0.97，95% CI 0.53 - 1.79，P = 0.93；病理类型，OR 0.97，95% CI 0.59 - 1.60，P = 0.91；临床分期，OR 1.48，95% CI 0.81 - 2.68，P = 0.2；淋巴结转移，OR 0.68，95% CI 0.13 - 3.63，P = 0.65；或分化程度，OR 1.01，95% CI 0.34 - 3.
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