Aberrant PTPRO Methylation in Tumor Tissues as a Potential Biomarker that Predicts Clinical Outcomes in Breast Cancer Patients
Background: Aberrant hypermethylation of gene promoter regions is a primary mechanism by which tumor suppressor genes become inactivated in breast cancer.Epigenetic inactivation of the protein tyrosine phosphatase receptor-type O gene (PTPRO) has been described in several types of cancer.Results: We screened primary breast cancer tissues for PTPRO promoter hypermethylation and assessed potential associations with pathological features and patient outcome.We also evaluated its potential as a breast cancer biomarker.PTPRO methylation was observed in 53 of 98 (54％) breast cancer tissues but not in adjacent normal tissue.Among matched peripheral blood samples from breast cancer patients, 33 of 98 (34％) exhibited methylated PTPRO in plasma.In contrast, no methylated PTPRO was observed in normal peripheral blood from 30 healthy individuals.PTPRO methylation was positively associated with lymph node involvement (P =0.014), poorly differentiated histology (P =0.037), depth of invasion (P =0.004), and HER2 amplification (P =0.001).Patients with PTPRO methylation showed significantly worse survival in both univariate (P =0.0001) and multivariate analyses (relative risk =3.8;95％ CI ”1.9 ～ 7.5”;P =0.0001).In addition, demethylation induced by 5-azacytidine led to gene reactivation in PTPRO-methylated and-silenced breast cancer cell lines.Conclusions: Tumor PTPRO methylation is a strong prognostic factor in breast cancer.Methylation of PTPRO silences its expression and plays an important role in breast carcinogenesis.The data we present here may provide insight into the development of novel therapies for breast cancer treatment.Additionally, detection of PTPRO methylation in peripheral blood of breast cancer patients may provide a noninvasive means to diagnose and monitor the disease.
李少英 李荣 罗荣城
Tranditional Chinese Medicine-Integrated Hospital, Southern Medical University;Department of Breast Tranditional Chinese Medicine-Integrated Hospital, Southern Medical University
国内会议
第八届中国肿瘤内科大会、第三届中国肿瘤医师大会暨中国抗癌协会肿瘤临床化疗专业委员会2014年学术年会
北京
英文
510-510
2014-07-02（万方平台首次上网日期，不代表论文的发表时间）