近日,，國際著名雜志PloS ONE在線刊登了江蘇省姜堰市人民醫(yī)院的研究人員的最新研究成果: "The prognostic role of RASSF1A promoter methylation in breast cancer: a meta-analysis of published data"。
文章中,，研究者薈萃分析后發(fā)現(xiàn)：RASSF1A啟動子區(qū)高甲基化的乳腺癌患者無論在"無進展生存期"（DFS） 還是"總生存時間"（OS）上均有顯著性統(tǒng)計學意義,，因此，RASSF1A甲基化的檢測是很有價值的臨床指標,，可以作為預后的獨立的危險因素,，值得進一步深入研究和關注。
乳腺癌的患者預后差別較大,，通常以"腫瘤大小,、腫瘤TNM分期、病理分級,、激素受體表達"等指標來預測患者的預后,，根據(jù)患者的腫瘤生物學特點選擇相應的治療，然而這些指標預測患者的預后力度還不夠,，不能夠針對個體患者進行分層,。使得預后差的患者及時接受治療，預后良好的患者避免接受不必要的治療,，從而避免不恰當治療帶來的毒副反應,。
乳腺癌的發(fā)生發(fā)展與癌基因的激活和抑癌基因的失活密切相關,。大量研究發(fā)現(xiàn),，抑癌基因的失活與其啟動子區(qū)甲基化密切相關。RASSF1A是其中一個重要的抑癌基因,。它的啟動子區(qū)過度甲基化后可使它的活性下降,，從而影響抑癌作用，因此影響乳腺癌的發(fā)生,、發(fā)展,。在這篇文章中，研究人員薈萃分析了來自8個國家總樣本量達到1795例的乳腺癌患者資料,，統(tǒng)計發(fā)現(xiàn)：過度甲基化的RASSF1A無論在"無進展生存期"（DFS） 還是"總生存時間"（OS）上均有顯著性統(tǒng)計學意義,，所以RASSF1A甲基化可以作為乳腺癌預后的一項獨立危險因素。
來自姜堰市人民醫(yī)院的崔林為這篇文章的通訊作者,。姜勇是該文章的第一作者,。陳文德、申仕海,、丁立東為該文的共同作者,。來自美國俄亥俄州立大學的著名學者Amanda Ewart Toland教授為本文審稿，并做同行評議,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0036780
The Prognostic Role of RASSF1A Promoter Methylation in Breast Cancer: A Meta-Analysis of Published Data
Yong Jiang1, Lin Cui1*, Wen-de Chen2, Shi-hai Shen2, Li-dong Ding2
Purpose
Epigenetic alterations have been investigated as prognostic indicators in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. We present the results of a meta-analysis of the associations between RASSF1A promoter methylation status and both disease free survival (DFS) and overall survival (OS) in female breast cancer.
Methods
Eligible studies were identified through searching the PubMed, Web of Science and Embase databases. Studies were pooled and summary hazard ratios (HR) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also carried out to evaluate publication bias.
Results
A total of 1795 patients from eight studies were included in the meta-analysis. There are eight studies which investigated DFS in 1795 cases. The relative hazard estimates ranged from 1.77–5.64 with a combined HR of 2.75 (95%CI 1.96–3.84). The HR of RASSF1A promoter methylation on DFS adjusted for other potential prognostic factors was 2.54 (95%CI 1.77–3.66). There has been five trials which analyzed the associations of RASSF1A promoter methylation status with OS in 1439 patients. The hazard estimates ranged from 1.21–6.90 with a combined random-effects estimates of 3.47 (95%CI 1.44–8.34). OS reported in multivariate analysis was evaluated in four series comprising 1346 cases and the summarized random-effects HR estimate was 3.35 (95%CI 1.14–9.85). Additionally, no publication bias was detected for both OS and DFS.
Conclusion
The results of this meta-analysis suggest that RASSF1A promoter hypermethylation confers a higher risk of relapse and a worse survival in patients with breast cancer. Large prospective studies are now needed to establish the clinical utility of RASSF1A promoter methylation..
