Transcriptome evolution from breast epithelial cells to basallike tumors

// Gabriel Santpere 1 , Ana Alcaraz-Sanabria 2 , Veronica Corrales-Sanchez 2 , Atanasio Pandiella 3 , Balazs Győrffy 4, 5 and Alberto Ocana 2, 6 1 Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA 2 Translational Research Unit and CIBERONC, Albacete University Hospital, Albacete, Spain 3 Cancer Research Center and CIBERONC, CSIC-University of Salamanca, Salamanca, Spain 4 MTA TTK Lendulet Cancer Biomarker Research Group, Budapest, Hungary 5 Semmelweis University 2nd Department of Pediatrics, Budapest, Hungary 6 Regional Biomedical Research Center (CRIB), Castilla La Mancha University, Albacete, Spain Correspondence to: Alberto Ocana, email: albertoo@sescam.jccm.es Keywords: breast cancer; transcriptomic evolution; carcinoma in situ Received: August 02, 2017      Accepted: November 14, 2017      Published: December 08, 2017 ABSTRACT In breast cancer, it is unclear the functional modifications at a transcriptomic level that are associated with the evolution from epithelial cells and ductal carcinoma in situ (DCIS) to basal-like tumors. By applying weighted gene co-expression network analysis (WGCNA), we identified 17 gene co-expression modules in normal, DCIS and basal-like tumor samples. We then correlated the expression pattern of these gene modules with disease progression from normal to basal-like tumours and found eight modules exhibiting a high and statistically significant correlation. M4 included genes mainly related to cell cycle/division and DNA replication like CCNA2 or CDK1. The M7 module included genes linked with the immune response showing top hub genes such as CD86 or PTPRC. M10 was found specifically correlated to DCIS, but not to basal-like tumor samples, and showed enrichment in ubiquitination or ubiquitin-like processes. We observed that genes in some of these modules were associated with clinical outcome and/or represented druggable opportunities, including AURKA, AURKB, PLK1, MCM2, CDK1, YWHAE, HSP90AB1, LCK, or those targeting ubiquitination. In conclusion, we describe relevant gene modules related to biological functions that can influence survival and be targeted pharmacologically.