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Gene expression signature involved in estrogen receptor status and prognosis of breast cancers

ABSTRACT: Fine needle aspiration biopsies (FNABs) of breast cancers were taken before and after surgeries from 16 patients. The cDNA microarray data were used to determine the gene expression profile responding to patient's clinical finding and tumor's pathological changes. A gene profile was generated as Estrogen Receptor Gene Signature (ERGS). The ERGS was verified in a reference dataset and correlated with patient's prognosis significantly. Keywords: Breast cancer, fine needle biopsy, estrogen receptor, prognostic gene signature Dye-swap technical replicates were included both FNABs taken before and after surgeries for every patient, then the four replicated array data per patient were combined for analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Wang Dong-Yu

PROVIDER: S-ECPF-GEOD-12080 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundEstrogens are known to regulate the proliferation of breast cancer cells and to modify their phenotypic properties. Identification of estrogen-regulated genes in human breast tumors is an essential step toward understanding the molecular mechanisms of estrogen action in cancer. To this end we generated and compared the Serial Analysis of Gene Expression (SAGE) profiles of 26 human breast carcinomas based on their estrogen receptor alpha (ER) status. Thus, producing a breast cancer SAGE database of almost 2.5 million tags, representing over 50,000 transcripts.ResultsWe identified 520 transcripts differentially expressed between ERalpha-positive (+) and ERalpha-negative (-) primary breast tumors (Fold change >or= 2; p < 0.05). Furthermore, we identified 220 high-affinity Estrogen Responsive Elements (EREs) distributed on the promoter regions of 163 out of the 473 up-modulated genes in ERalpha (+) breast tumors. In brief, we observed predominantly up-regulation of cell growth related genes, DNA binding and transcription factor activity related genes based on Gene Ontology (GO) biological functional annotation. GO terms over-representation analysis showed a statistically significant enrichment of various transcript families including: metal ion binding related transcripts (p = 0.011), calcium ion binding related transcripts (p = 0.033) and steroid hormone receptor activity related transcripts (p = 0.031). SAGE data associated with ERalpha status was compared with reported information from breast cancer DNA microarrays studies. A significant proportion of ERalpha associated gene expression changes was validated by this cross-platform comparison. However, our SAGE study also identified novel sets of genes as highly expressed in ERalpha (+) invasive breast tumors not previously reported. These observations were further validated in an independent set of human breast tumors by means of real time RT-PCR.ConclusionThe integration of the breast cancer comparative transcriptome analysis based on ERalpha status coupled to the genome-wide identification of high-affinity EREs and GO over-representation analysis, provide useful information for validation and discovery of signaling networks related to estrogen response in this malignancy.

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Gene expression signature involved in estrogen receptor status and prognosis of breast cancers

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