Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: 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, ccSAGPs), 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 ccSAGPs (BCR-ccSAGPs). We isolated and characterized the sense-antisense gene classifier (SAGC) 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 SAGC was effective in identification of BC patients with the most aggressive disease. Independently, we validated the SAGC 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).

ORGANISM(S): Homo sapiens

SUBMITTER: Surya Pavan Yenamandra

PROVIDER: E-GEOD-61304 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Breast carcinoma (BC) is the leading cause of death in women worldwide, making up 23% of all cancers in women, with 1.38 million new cases worldwide annually and responsible for 460,000 deaths. Despite the significant advances in the identification of molecular markers and different modalities of treatment in primary BC, the ability to predict the metastatic behavior in breast cancer is still limited. The purpose of this study was to help identify novel molecular markers associated with clinical outcome in a cohort of Brazilian BC patients. We generated global gene expression profiles from 24 patients with invasive ductal BC followed for â¥ 5-years, including 15 samples from patients classified as presenting good prognosis based on traditional markers and clinical criteria and 9 patients that developed metastasis. We identified a set of 58 differentially expressed genes (p â¤0.01) between groups of patients with good and poor prognosis. Up-regulation of B3GNT7, PPM1D, TNKS2, PHB and GTSE1 in patients with poor prognosis was confirmed by quantitative RT-PCR in an independent sample set from patients with BC (47 with good prognosis and 8 that presented metastasis). Expression of BAD protein was investigated by immunohistochemistry in 1276 BC samples and confirmed the reduced expression levels in metastatic cases observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinoma samples according to clinical course and progression of the disease. Global expression profiles from 38 ductal breast tumor patient samples were used to search for molecular signatures correlated with current prognostic markers. A subset of 24 cases comprising 15 patients that remained free of disease after surgery and 9 patients that developed metastasis was used to identify candidate biomarkers associated with metastatic progression. Candidates were subsequently validated in additional independent samples by RT-qPCR or immunohistochemistry.

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

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