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Breast Cancer Research and Treatment

, Volume 160, Issue 2, pp 371–383 | Cite as

Integrated analysis of gene expression and methylation profiles of 48 candidate genes in breast cancer patients

  • Zibo Li
  • Jianfu Heng
  • Jinhua Yan
  • Xinwu Guo
  • Lili Tang
  • Ming Chen
  • Limin Peng
  • Yepeng Wu
  • Shouman Wang
  • Zhi Xiao
  • Zhongping Deng
  • Lizhong Dai
  • Jun WangEmail author
Epidemiology

Abstract

Purpose

Gene-specific methylation and expression have shown biological and clinical importance for breast cancer diagnosis and prognosis. Integrated analysis of gene methylation and gene expression may identify genes associated with biology mechanism and clinical outcome of breast cancer and aid in clinical management.

Methods

Using high-throughput microfluidic quantitative PCR, we analyzed the expression profiles of 48 candidate genes in 96 Chinese breast cancer patients and investigated their correlation with gene methylation and associations with breast cancer clinical parameters.

Results

Breast cancer-specific gene expression alternation was found in 25 genes with significant expression difference between paired tumor and normal tissues. A total of 9 genes (CCND2, EGFR, GSTP1, PGR, PTGS2, RECK, SOX17, TNFRSF10D, and WIF1) showed significant negative correlation between methylation and gene expression, which were validated in the TCGA database. Total 23 genes (ACADL, APC, BRCA2, CADM1, CAV1, CCND2, CST6, EGFR, ESR2, GSTP1, ICAM5, NPY, PGR, PTGS2, RECK, RUNX3, SFRP1, SOX17, SYK, TGFBR2, TNFRSF10D, WIF1, and WRN) annotated with potential TFBSs in the promoter regions showed negative correlation between methylation and expression. In logistics regression analysis, 31 of the 48 genes showed improved performance in disease prediction with combination of methylation and expression coefficient.

Conclusions

Our results demonstrated the complex correlation and the possible regulatory mechanisms between DNA methylation and gene expression. Integration analysis of methylation and expression of candidate genes could improve performance in breast cancer prediction. These findings would contribute to molecular characterization and identification of biomarkers for potential clinical applications.

Keywords

Breast cancer Methylation Gene expression Microfludic PCR Next-generation sequencing 

Notes

Acknowledgments

This work was supported in part by grants from the Natural Science Foundation of China (No. 81272296 and 81372228), the Scientific Project of China Hunan Provincial Science and Technology Department (No. 2012SK2013), and the Major Special Projects of the Science and Technology Bureau of Changsha, China (No. K1204017-31 and K1306011-31). Zibo Li was supported by the Hunan Province Postgraduate Student Scientific Innovation Project, China (No. CX2013B087).

Compliance with ethical standards

Conflict of interest

Xingwu Guo, Limin Peng, Ming Chen, Zhongping Deng, and Lizhong Dai are employees of Sanway Gene Technology Inc.

Ethical standards

We declare that the experiments performed in this study comply with the current laws of the People’s Republic of China.

Supplementary material

10549_2016_4004_MOESM1_ESM.doc (64 kb)
Online Resource Methods (DOC 63 kb)
10549_2016_4004_MOESM2_ESM.doc (96 kb)
Online Resource Table 1 (DOC 96 kb)
10549_2016_4004_MOESM3_ESM.xls (178 kb)
Online Resource Table 2 (XLS 177 kb)
10549_2016_4004_MOESM4_ESM.xls (30 kb)
Online Resource Table 3 (XLS 30 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Zibo Li
    • 1
  • Jianfu Heng
    • 1
  • Jinhua Yan
    • 1
  • Xinwu Guo
    • 2
  • Lili Tang
    • 3
  • Ming Chen
    • 2
  • Limin Peng
    • 2
  • Yepeng Wu
    • 1
  • Shouman Wang
    • 3
  • Zhi Xiao
    • 3
  • Zhongping Deng
    • 2
    • 4
    • 5
  • Lizhong Dai
    • 2
    • 4
    • 5
  • Jun Wang
    • 1
    Email author
  1. 1.The State Key Laboratory of Medical Genetics & School of Life SciencesCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Sanway Gene Technology Inc.ChangshaPeople’s Republic of China
  3. 3.Department of Breast Surgery, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  4. 4.Research Center for Technologies in Nucleic Acid-Based DiagnosticsChangshaPeople’s Republic of China
  5. 5.Research Center for Technologies in Nucleic Acid-Based Diagnostics and TherapeuticsChangshaPeople’s Republic of China

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