A hedgehog pathway-dependent gene signature is associated with poor clinical outcomes in Luminal A breast cancer
Abstract
High expression of glioma-associated oncogene homolog-1 (GLI1) is associated with poor prognosis in estrogen receptor (ER) positive breast cancers. We sought to define a GLI1-dependent gene signature in ER-positive tumors that could further stratify patients at higher risk for disease recurrence and potentially lead to novel combination therapies. We identified an inverse correlation between GLI1 expression and distant disease-free survival (DFS) using a dataset developed at MD Anderson Cancer Center (Hatzis dataset) containing clinical data from 508 breast cancer patients. Using a qPCR-based microarray platform, we identified genes differentially regulated by GLI1 in MCF7 cells and then determined if expression of these genes correlated with GLI1 expression in patient tumor samples. Statistical comparison between the groups was performed by ANOVA. Direct comparison of two groups was done by a two-tailed t test. Correlations between variables were done by Pearson's method. Expression of GLI1 and its target genes correlated significantly with worse distant DFS in breast cancer patients with Luminal A molecular subtype. Particularly, co-expression of GLI1 with EGFR and/or SNAI1, two of the identified GLI1 targets, was predictive ...Continue Reading
References
Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogen
Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line
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