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中国中部地区原发性胃癌中RASSF1A表达降低与启动子甲基化的关联

Association of diminished expression of RASSF1A with promoter methylation in primary gastric cancer from patients of central China.

作者信息

Ye Mei, Xia Bing, Guo Qiusha, Zhou Feng, Zhang Xiaolian

机构信息

Department of Internal Medicine & Geriatrics, Research Centre of Digestive Diseases, Zhongnan Hospital, Wuhan University, PR China.

出版信息

BMC Cancer. 2007 Jul 3;7:120. doi: 10.1186/1471-2407-7-120.

DOI:10.1186/1471-2407-7-120
PMID:17608924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1925110/
Abstract

BACKGROUND

Although methylation-mediated inactivation of expression of RASSF1A, a candidate tumor suppressor gene, has been observed in several human cancers, the data concerning alteration of RASSF1A expression and methylation in Chinese primary gastric cancer are scarce. Moreover, direct evidence showing the association between protein expression of RASSF1A and primary human cancers is lacking. The aim of this study was to investigate RASSF1A expression in tissue of primary gastric cancer (GC) at mRNA and protein levels, and to establish the possible relationship between DNA methylation status and protein expression of RASSF1A in Chinese.

METHODS

Fifty-four patients with primary gastric cancers were included in the study of RASSF1A mRNA expression and methylation status between the cancer tissue and the corresponding adjacent normal tissue. 20 out of 54 patients were included for study of RASSF1A protein expression. The expression of RASSF1A at mRNA and protein levels was determined by RT-PCR and Western-blotting, respectively. The RASSF1A promoter methylation was detected by methylation-specific PCR.

RESULTS

RASSF1A mRNA and protein expressions in GC were reduced significantly with comparison to the corresponding normal tissues (OD value: 0.2589 +/- 0.2407 vs 0.5448 +/- 0.2971, P < 0.0001; 0.1874 +/- 0.0737 vs 0.6654 +/- 0.2201, P < 0.0001, respectively). Methylation frequency of RASSF1A in primary GC is higher than that in the corresponding normal tissues (66.7% vs. 14.8%, P < 0.0001). Furthermore, RASSF1A mRNA expression in methylation group of GC was further reduced when compared to the unmethylation group of GC (0.1384 +/- 0.1142 vs. 0.5018 +/- 0.2463, P < 0.0001).

CONCLUSION

Expression of RASSF1A was reduced in tissue of GC at mRNA and protein levels. Diminished expression of RASSF1A was associated with the promoter methylation.

摘要

背景

尽管在几种人类癌症中已观察到候选抑癌基因RASSF1A的甲基化介导的表达失活,但关于中国原发性胃癌中RASSF1A表达和甲基化改变的数据却很少。此外,缺乏显示RASSF1A蛋白表达与原发性人类癌症之间关联的直接证据。本研究的目的是在mRNA和蛋白质水平上研究原发性胃癌(GC)组织中RASSF1A的表达,并在中国人群中确定RASSF1A的DNA甲基化状态与蛋白质表达之间的可能关系。

方法

54例原发性胃癌患者纳入研究,分析癌组织和相应癌旁正常组织中RASSF1A mRNA表达和甲基化状态。54例患者中的20例纳入RASSF1A蛋白表达研究。分别通过RT-PCR和Western印迹法测定RASSF1A在mRNA和蛋白质水平的表达。通过甲基化特异性PCR检测RASSF1A启动子甲基化。

结果

与相应正常组织相比,GC中RASSF1A mRNA和蛋白质表达显著降低(OD值:0.2589±0.2407对0.5448±0.2971,P<0.0001;0.1874±0.0737对0.6654±0.2201,P<0.0001)。原发性GC中RASSF1A的甲基化频率高于相应正常组织(66.7%对14.8%,P<0.0001)。此外,与GC未甲基化组相比,GC甲基化组中RASSF1A mRNA表达进一步降低(0.1384±0.1142对0.5018±0.2463,P<0.0001)。

结论

GC组织中RASSF1A在mRNA和蛋白质水平表达降低。RASSF1A表达降低与启动子甲基化有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/6769c055d06c/1471-2407-7-120-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/86b040b853de/1471-2407-7-120-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/772243f16e9f/1471-2407-7-120-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/6769c055d06c/1471-2407-7-120-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/86b040b853de/1471-2407-7-120-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/772243f16e9f/1471-2407-7-120-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2bc/1925110/6769c055d06c/1471-2407-7-120-3.jpg

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