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CHD1基因启动子异常甲基化可能与乳腺癌发病机制有关:一项荟萃分析。

Aberrant promoter methylation of the CHD1 gene may contribute to the pathogenesis of breast cancer: a meta-analysis.

作者信息

Gu Xi, Xue Jin-Qi, Zhu Xi, Ye Ming-Shi, Zhang Wen-Hai

机构信息

Department of Breast Surgery, Shengjing Hospital, China Medical University, Sanhao Street No. 36, Heping District, Shenyang, 110004, People's Republic of China.

出版信息

Tumour Biol. 2014 Sep;35(9):9395-404. doi: 10.1007/s13277-014-2235-z. Epub 2014 Jun 22.

DOI:10.1007/s13277-014-2235-z
PMID:24952891
Abstract

Cadherin-1 (CHD1), as an invasion suppressor gene, could suppress tumor cell invasion and metastasis in various tumors, but reduced CHD1 levels, resulting from epigenetic silencing, are common in poorly differentiated, advanced stage carcinomas. This meta-analysis was performed to evaluate the relationships between promoter methylation of CHD1 and breast cancer. Relevant studies were retrieved from the Web of Science (1945 ~ 2013), the Cochrane Library (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) using a systematic literature search. Results were summarized by meta-analyses, conducted using the STATA software (version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated. In the present meta-analysis, 9 cohort studies with a total of 425 patients with breast cancer were included. Our meta-analysis results demonstrated that the frequency of CHD1 promoter methylation in cancer tissues was significantly higher than that in normal tissues, adjacent tissues, and benign tissues (cancer tissue vs. normal tissue OR = 30.87, 95 % CI = 16.76 ~ 56.86, P < 0.001; cancer tissue vs. adjacent tissue OR = 23.30, 95 % CI = 12.85 ~ 42.26, P < 0.001; cancer tissue vs. benign tissue OR = 2.94, 95 % CI = 1.60 ~ 5.40, P < 0.001; respectively). Ethnicity-stratified analysis indicated that aberrant CHD1 promoter methylation was strongly correlated with breast cancer among both Asians and Caucasians in the majority of subgroups. Our results suggest that aberrant promoter methylation of the CHD1 gene may have a high frequency in breast cancer tissues. Thus, CHD1 methylation could be correlated with the pathogenesis of breast cancer.

摘要

钙黏蛋白-1(CHD1)作为一种侵袭抑制基因,可抑制多种肿瘤中的肿瘤细胞侵袭和转移,但在低分化、晚期癌中,由表观遗传沉默导致的CHD1水平降低很常见。本荟萃分析旨在评估CHD1启动子甲基化与乳腺癌之间的关系。通过系统文献检索,从科学网(1945年至2013年)、考克兰图书馆(2013年第12期)、PubMed(1966年至2013年)、EMBASE(1980年至2013年)、CINAHL(1982年至2013年)和中国生物医学数据库(CBM)(1982年至2013年)中检索相关研究。使用STATA软件(版本12.0,美国德克萨斯州大学站Stata公司)进行荟萃分析来总结结果。计算比值比(OR)和95%置信区间(95%CI)。在本荟萃分析中,纳入了9项队列研究,共425例乳腺癌患者。我们的荟萃分析结果表明,癌组织中CHD1启动子甲基化的频率显著高于正常组织、邻近组织和良性组织(癌组织与正常组织相比,OR = 30.87,95%CI = 16.76至56.86,P < 0.001;癌组织与邻近组织相比,OR = 23.30,95%CI = 12.85至42.26,P < 0.001;癌组织与良性组织相比,OR = 2.94,95%CI = 1.60至5.40,P < 0.001;分别)。按种族分层分析表明,在大多数亚组中,异常的CHD1启动子甲基化在亚洲人和白种人中均与乳腺癌密切相关。我们的结果表明,CHD1基因的异常启动子甲基化在乳腺癌组织中可能具有较高频率。因此,CHD1甲基化可能与乳腺癌的发病机制相关。

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