Expression profiling by array Third-party reanalysis
Summary
Abstract
Aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis primarily in estrogen receptor positive (ER(+)) breast cancers and activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of *STAT3* in ER(+) breast cancers are* *through multiple interacting regulatory pathways including STAT3-MYC, STAT3-ER , STAT3-MYC-ER interactions and the direct action of activated STAT3. These results predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ER and STAT3 in regulating their shared target gene-*METAP2* is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the *STAT3* network and a robust one in a subset of patients. *VEGFA*, *ABL1*, *LYN*, *IGF2R* and* STAT3* are suggested therapeutic targets for further study based upon the degree of differential expression in our model.
181 surgical specimens of primary infiltrating ductal carcinoma (IDC) were obtained from patients who underwent surgery at National Taiwan University Hospital (NTUH) between 1998 and 2007. They include 90 ER(+) IDCs and 91 ER(-) IDCs. Tissue samples were excised, snap frozen in liquid nitrogen, and stored at -80℃. Breast cancer samples containing relatively pure cancer as defined by greater than 50% tumor cells per high-power field examined in an adjacent section of tumor sample were for this study (Lien HC, et al. Oncogene 2007; 26: 7859-71). Twenty five non-tumor samples were surgically taken from breast cancer patients in 181 IDC patients to generate 25 gene expression profiles as a control in this study. All patients had given informed consent according to the guidelines approved by the Institutional Review Board at NTUH.
The matrix file linked to the bottom of this Series includes reanalyzed data from the 119 Samples of this Series and 87 Samples from Series GSE9309 and GSE17040.
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