Dataset Information

The prognostic role of RASSF1A promoter methylation in breast cancer: a meta-analysis of published data.

ABSTRACT:

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.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC3355150 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

The prognostic role of RASSF1A promoter methylation in breast cancer: a meta-analysis of published data.

Jiang Yong Y Cui Lin L Chen Wen-de WD Shen Shi-hai SH Ding Li-dong LD

PloS one 20120517 5

<h4>Purpose</h4>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.<h4>Methods</h4>Eligible studies were identified through searching the PubMed, Web of Science and Embase ...[more]

PMID: 22615811

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Project description:It has been shown in some articles that genetic and epigenetic abnormalities cannot only be found in tumor tissues but also in adjacent regions that appear histologically normal. This phenomenon is metaphorically called field cancerization or field defect. Field cancerization is regarded as clinically significant because it is assumed to be an important factor in local recurrence of cancer. As the field showing these molecular abnormalities may not be removed completely by surgery, these changes might lead to neoplasms and subsequent transformation to a tumor. We aimed to investigate the applicability of the methylation status of six tumor suppressor genes as biomarkers for detecting field cancerization in breast cancer.The promoter methylation status of CCND2, DAPK1, GSTP1, HIN-1, MGMT and RASSF1A was determined by methylation-sensitive high-resolution melting (MS-HRM) analysis. MS-HRM methods for CCND2, MGMT and RASSF1A were developed in-house, primer sequences for DAPK1, GSTP1 and HIN-1 have already been published. Biopsy samples were taken from tumor, tumor-adjacent and tumor-distant tissue from 17 breast cancer patients. Normal breast tissues of four healthy women served as controls.All MS-HRM methods proved to be very sensitive. LODs were in the range from 0.1 to 1.5 %, LOQs ranged from 0.3 to 5.3 %. A total of 94 %, 82 % and 65 % of the tumors showed methylation of RASSF1A, HIN-1 and MGMT promoters, respectively. The methylation status of these promoters was significantly lower in tumor-distant tissues than in tumor tissues. Tumor-adjacent tissues showed higher methylation status of RASSF1A, HIN-1 and MGMT promoters than tumor-distant tissues, indicating field cancerization. The methylation status of the HIN-1 promoter in tumor-adjacent tissues was found to correlate strongly with that in the corresponding tumors (r?=?0.785, p?<?0.001), but not with that in the corresponding tumor-distant tissues (r?=?0.312, p?=?0.239).Among the gene promoters investigated, the methylation status of the HIN-1 promoter can be considered the best suitable biomarker for detecting field cancerization. Further investigation is needed to test whether it can be used for defining surgical margins in order to prevent future recurrence of breast cancer.

Dataset Information

The prognostic role of RASSF1A promoter methylation in breast cancer: a meta-analysis of published data.

Purpose

Methods

Results

Conclusion

Publications

The prognostic role of RASSF1A promoter methylation in breast cancer: a meta-analysis of published data.

Similar Datasets

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