C-RAF would preferentially promote anti-apoptotic signaling whilst B-RAF, through the MEK-ERK module, would modulate proliferation of neuroepithelial progenitors.
Among the seven defined modules, proliferation (Wilcoxon test, P = 0.064), HER2 (Wilcoxon test, P = 0.0057), tumor invasion and metastasis (Wilcoxon test, P = 1.0 × 10-5), ER signaling (Wilcoxon test, P = 1.3 × 10-8) and immune response (Wilcoxon test, P = 0.16) displayed significant differences or a tendency towards differences between the two subgroups.
Specifically, we validate in vivo the association of the miR-17-92 miR-17-92 miR-17-92tion in breast cancer, in agreemoduleito the same association observed in tumor cell lines [47].
Interestingly, a majority of genes in the CSR centroid did not show clear co-expression with any of eight different co-expressed gene expression modules, including two proliferation modules (Checkpoint and M-phase) (Fredlund et al. Manuscript in preparation) (Figure 6A).
Group-wise effects on Ki-67 staining intensity for genes in the two proliferation modules were analyzed per module by comparing the mean module Ki-67 intensity to a random intensity distribution based on 10,000 sampled gene groups of the same size as the assayed module.
Interestingly, many of these individually prognostic genes were also highly correlated with the proliferation module prototype and not with the other two modules, suggesting that proliferation may be the common driving force of several prognostic signatures.
Interestingly, this HRneg/Tneg multigene index lacks any proliferation module and shows modest but significant correlations with the previously reported IR, IFN, and STAT1 module genes.
Two other modules consisting of protein processing and immunity‐related genes, respectively, were found to be slightly correlated with the cell proliferation module.
The proliferation module classifier showed better sensitivity but lower specificity than the one based on statistically most informative markers.
