Novel bio-marker discovery for stratification and prognosis of breast cancer patients

The study entails novel bio-marker discovery of Tumor Aggressive Grade signature (TAGs) genes and their role in recurrence free survival of breast cancer (BC) patients. Current BC dataset was used for co-expression analysis of TAGs genes and their role in BC progression. Additionally, recent findings have suggested an importance of structural organization of sense-antisense gene pairs (SAGPs) for transcription, post-transcriptional and post-translational events and their associations with cancer and disease. We studied SAGPs in which both gene partners are protein encoding genes (coding-coding SAGPs), their role in human BC development and demonstrated their potential for BC stratification and prognosis. Based on gene expression and correlation analyses we identified the robust set of breast cancer-relevant SAGPs (BCR-SAGPs). We isolated and characterized the sense-antisense gene signature (SAGS) and evaluated its prognostic potential in various gene expression datasets comprising 1161 BC patients. The methods used included the Cox proportional survival analysis, statistical analysis of clinicopathologic parameters and differential gene expression. The SAGS was effective in identification of BC patients with the most aggressive disease. Independently, we validated the SAGS using 58 RNA samples of breast cancer tumors purchased from OriGene Technologies (Rockville, MD). Sixty two total RNA samples from breast tumors and normal breast epithelium have been purchased from OriGene Technologies in March, 2011. Four RNA samples were obtained from normal individuals. Among 58 breast tumors (58 patients) 56 were diagnosed as ductal breast adenocarcinoma, 1 - as lobular breast adenocarcinoma and 1 - as squamous cell carcinoma. Gene expression data for all the samples were quantified by using whole-genome RNA microarrays (HG-U133 plus 2.0, Affymetrix).