PrP mRNA levels were enriched in the basal subtype and were associated with poor prognosis in breast cancer patients.
Specifically, tumors with high S14 expression were significantly more likely to represent the luminal versus basal subtype, and were more likely to be ER+ than ER−.
In several breast cancer gene expression profiling datasets, MELK mRNA expression was higher in the basal subtype, and was associated with poor prognosis and early metastasis – these observations have been made in part by others previously.
In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival.
Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis.
Clusters C and D showed enrichment for the basal-like subtype and were associated to higher proliferation, although Cluster C included tumors with high CD44S expression and of luminal B and HER2-enriched subtype.
The validity of the claudin-low sample cluster was confirmed by parsing the dendogram with SigClust [ 22] (P < 0.001); notably, this clustering analysis placed the claudin-low tumors in close proximity to the basal-like subtype and was composed of 32 arrays, representing 32 patients (~12% of all patients).
For instance, FOXA1 is a key determinant of estrogen receptor function [ 42] and negatively correlates with tumor size, tumor grade and basal-subtype, and it is an independent predictor of breast cancer survival [ 43].
However, it also is apparent that the basal subtype is a heterogeneous group (Vincent-Salomon et al, 2007), and further analysis is required to more accurately define the precise nature of the tumours in these women.
miR-29c also had the lowest expression in the basal subtype, which is the most aggressive form of breast cancer.
