In silico discovery of mitosis regulation networks associated with early distant metastases in estrogen receptor positive breast cancers

Yuriy Gusev, Rebecca B. Riggins, Krithika Bhuvaneshwar, Robinder Gauba, Laura Sheahan, Robert Clarke, Subha Madhavan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The aim of this study was to perform comparative analysis of multiple public datasets of gene expression in order to identify common genes as potential prognostic biomarkers. Additionally, the study sought to identify biological processes and pathways that are most significantly associated with early distant metastases (< 5 years) in women with estrogen receptor-positive (ER+) breast tumors. Datasets from three published studies were selected for in silico analysis of gene expression profiles of ER+ breast cancer, using time to distant metastasis as the clinical endpoint. A subset of 44 differently expressed genes (DEGs) was found common to all three studies and characterized by mitotic checkpoint genes and pathways that regulate mitotic spindle and chromosome dynamics. DEG promoter regions were enriched with NFY binding sites. Analysis of miRNA target sites identified significant enrichment of miR-192, miR-193B, and miR-16-1 targets. Aberrant mitotic regulation could drive increased genomic instability leading to a progression towards an early onset metastatic phenotype. The relative importance of mitotic instability may reflect the clinical utility of mitotic poisons in metastatic breast cancer, including poisons such as the taxanes, epothilones, and vinca alkaloids.

Original languageEnglish (US)
Pages (from-to)31-51
Number of pages21
JournalCancer Informatics
Volume12
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Early distant metastasis
  • Estrogen receptor alpha-positive
  • Mitotic checkpoint signaling
  • Mitotic regulation network
  • microRNA targets

Fingerprint Dive into the research topics of 'In silico discovery of mitosis regulation networks associated with early distant metastases in estrogen receptor positive breast cancers'. Together they form a unique fingerprint.

Cite this