Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome

BMC Cancer

Research Article

Priya B Shetty¹  Susan G Hilsenbeck²  Robert C Bast³  Jia Xu⁴  Weiwei Feng⁵  Yinhua Yu⁵  Jean-Pierre J Issa⁶  Carol Chenault⁷ 

[1] Dan L Duncan Cancer Center, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA;Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, 44106, Cleveland, OH, USA;Dan L Duncan Cancer Center, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA;Lester and Sue Smith Breast Center, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA;Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA;Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA;Graduate School of Biomedical Science, The University of Texas, 77030, Houston, TX, USA;Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA;Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China;Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA;Fels Institute for Cancer and Molecular Biology, Temple University, 3307 North Broad Street, 19140, Philadelphia, PA, USA;Lester and Sue Smith Breast Center, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA;

关键词: Breast Cancer;    Estrogen Receptor;    Progesterone Receptor;    Methylation Level;    Early Stage Breast Cancer;   

DOI  :  10.1186/1471-2407-12-243

 received in 2011-04-19, accepted in 2012-06-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAberrant promoter CpG island hypermethylation is associated with transcriptional silencing. Tumor suppressor genes are the key targets of hypermethylation in breast cancer and therefore may lead to malignancy by deregulation of cell growth and division. Our previous pilot study with pairs of malignant and normal breast tissues identified correlated methylation of two pairs of genes - HIN-1/RASSFIA and RIL/CDH13 - with expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 (HER2). To determine the impact of methylation on clinical outcome, we have conducted a larger study with breast cancers for which time to first recurrence and overall survival are known.MethodsTumors from 193 patients with early stage breast cancer who received no adjuvant systemic therapy were used to analyze methylation levels of RIL, HIN-1, RASSF1A and CDH13 genes for associations with known predictive and prognostic factors and for impact on time to first recurrence and overall survival.ResultsIn this study, we found that ER was associated with RASSF1A methylation (p < 0.001) and HIN-1 methylation (p = 0.002). PR was associated with RIL methylation (p = 0.012), HIN-1 (p = 0.002), and RASSF1A methylation (p = 0.019). Tumor size was associated with RIL and CDH13 methylation (both p = 0.002), and S-phase was associated with RIL methylation (p = 0.036). Only RASSF1A was associated with worse time to first recurrence (p = 0.045) and worse overall survival (p = 0.016) after adjusting for age, tumor size, S-phase, estrogen receptor and progesterone receptor.ConclusionsMethylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancers was associated with clinical characteristics, but only RASSF1A methylation was associated with time to first recurrence and overall survival. Our data suggest that RASSF1A methylation could be a potential prognostic biomarker.

【 授权许可】

Unknown   
© Xu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.