Identification of genetic and epigenetic variants associated with breast cancer prognosis by integrative bioinformatics analysis

Arunima Shilpi, Yingtao Bi, Segun Jung, Samir K. Patra, Ramana V. Davuluri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Introduction: Breast cancer being a multifaceted disease constitutes a wide spectrum of histological and molecular variability in tumors. However, the task for the identification of these variances is complicated by the interplay between inherited genetic and epigenetic aberrations. Therefore, this study provides an extrapolate outlook to the sinister partnership between DNA methylation and single-nucleotide polymorphisms (SNPs) in relevance to the identification of prognostic markers in breast cancer. The effect of these SNPs on methylation is defined as methylation quantitative trait loci (meQTL).Materials and methods: We developed a novel method to identify prognostic gene signatures for breast cancer by integrating genomic and epigenomic data. This is based on the hypothesis that multiple sources of evidence pointing to the same gene or pathway are likely to lead to reduced false positives. We also apply random resampling to reduce overfitting noise by dividing samples into training and testing data sets. Specifically, the common samples between Illumina 450 DNA methylation, Affymetrix SNP array, and clinical data sets obtained from the Cancer Genome Atlas (TCGA) for breast invasive carcinoma (BRCA) were randomly divided into training and test models. An intensive statistical analysis based on log-rank test and Cox propor-tional hazard model has established a significant association between differential methylation and the stratification of breast cancer patients into high- and low-risk groups, respectively.Results: The comprehensive assessment based on the conjoint effect of CpG–SNP pair has guided in delaminating the breast cancer patients into the high- and low-risk groups. In particular, the most significant association was found with respect to cg05370838–rs2230576, cg00956490–rs940453, and cg11340537–rs2640785 CpG–SNP pairs. These CpG–SNP pairs were strongly associated with differential expression of ADAM8, CREB5, and EXPH5 genes, respectively. Besides, the exclusive effect of SNPs such as rs10101376, rs140679, and rs1538146 also hold significant prognostic determinant.Conclusions: Thus, the analysis based on DNA methylation and SNPs have resulted in the identification of novel susceptible loci that hold prognostic relevance in breast cancer.

Original languageEnglish (US)
JournalCancer Informatics
StatePublished - Jan 9 2017


  • DNA methylation
  • MeQTLs
  • Overall survival
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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