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 Here,we report that 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.
Protein tyrosine phosphatase receptor-type O (PTPRO) Methylation Breast cancer Clinical outcome Biomarker
Shao-ying LI Rong LI Yu-li CHEN Li-kuang XIONG Hui-Lin WANG Lei Rong Rong-Cheng Luo
Cancer Center,Southern Medical University,Guangzhou,510315,China
国内会议
第五届国际中医、中西医结合肿瘤学术交流大会暨第十四届全国中西医结合肿瘤学术大会
广州
英文
1-14
2014-07-01（万方平台首次上网日期，不代表论文的发表时间）