title: Integrated analysis of gene expression and methylation profiles of 48 candidate genes in breast cancer patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China.
authors.forename: Zibo
authors.initials: Z
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China.
authors.forename: Jianfu
authors.initials: J
authors.lastname: Heng
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Yan
authors.affiliation: Sanway Gene Technology Inc., Changsha, 410205, Hunan, People's Republic of China.
authors.forename: Xinwu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tang
authors.affiliation: Sanway Gene Technology Inc., Changsha, 410205, Hunan, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Sanway Gene Technology Inc., Changsha, 410205, Hunan, People's Republic of China.
authors.forename: Limin
authors.initials: L
authors.lastname: Peng
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China.
authors.forename: Yepeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Shouman
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Sanway Gene Technology Inc., Changsha, 410205, Hunan, People's Republic of China.|Research Center for Technologies in Nucleic Acid-Based Diagnostics, Changsha, Hunan, 410205, People's Republic of China.|Research Center for Technologies in Nucleic Acid-Based Diagnostics and Therapeutics, Changsha, 410205, Hunan, People's Republic of China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Sanway Gene Technology Inc., Changsha, 410205, Hunan, People's Republic of China.|Research Center for Technologies in Nucleic Acid-Based Diagnostics, Changsha, Hunan, 410205, People's Republic of China.|Research Center for Technologies in Nucleic Acid-Based Diagnostics and Therapeutics, Changsha, 410205, Hunan, People's Republic of China.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Dai
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China. junwang@csu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D058977:Molecular Sequence Annotation; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast cancer; Gene expression; Methylation; Microfludic PCR; Next-generation sequencing