Integrated analysis of promoter methylation and expression of telomere related genes in breast cancer

Abstract

// Jianfu Heng 1 , Fan Zhang 1 , Xinwu Guo 2 , Lili Tang 3 , Limin Peng 2 , Xipeng Luo 2 , Xunxun Xu 2 , Shouman Wang 3 , Lizhong Dai 2, 4, 5 , Jun Wang 1 1 The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, 410013, China 2 Sanway Gene Technology Inc., Changsha, Hunan, 410205, China 3 Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China 4 Research Center for Technologies in Nucleic Acid-Based Diagnostics, Changsha, Hunan, 410205, China 5 Research Center for Technologies in Nucleic Acid-Based Diagnostics and Therapeutics, Changsha, Hunan, 410205, China Correspondence to: Jun Wang, email: junwang@csu.edu.cn Keywords: breast cancer, telomere, methylation, gene expression, biomarker Received: December 09, 2016     Accepted: February 07, 2017     Published: March 09, 2017 ABSTRACT Telomeres at the ends of eukaryotic chromosomes play a critical role in tumorgenesis. Using microfluidic PCR and next-generation bisulfite sequencing technology, we investigated the promoter methylation of 29 telomere related genes in paired tumor and normal tissues from 184 breast cancer patients. The expression of significantly differentially methylated genes was quantified using qPCR method. We observed that the average methylation level of the 29 telomere related genes was significant higher in tumor than that in normal tissues ( P = 4.30E-21). A total of 4 genes ( RAD50, RTEL, TERC and TRF1 ) showed significant hyper-methylation in breast tumor tissues. RAD51D showed significant methylation difference among the four breast cancer subtypes. The methylation of TERC showed significant association with ER status of breast cancer. The expression profiles of the 4 hyper-methylated genes showed significantly reduced expression in tumor tissues. The integration analysis of methylation and expression of these 4 genes showed a good performance in breast cancer prediction (AUC = 0.947). Our results revealed the methylation pattern of telomere related genes in breast cancer and suggested a novel 4-gene panel might be a valuable biomarker for breast cancer diagnosis.