Table 2.

Top Upstream Regulators of mRNA signature ${\gamma }_1$ for ovarian cancer

Upstream regulator	Predicted state	Activation score	Intersection P-value	Number of targets
IL4	Activated	2.115	2.115E-20	40
OSM	Activated	2.616	2.41E-08	21
Stat5(A/B)	Activated	2.630	6.50E-08	9

IPA identified IL4 as the top upstream regulator of the ${\mathit{\gamma }}_1$ signature that directly targeted 40 genes in the signature (Score=2.115, p=2.115E-20). These 40 genes formed a mRNA signature, φ ⁽⁴⁰⁾_IL4, that was “anchored” upstream by IL4 with expression patterns that implied the up-regulation of this gene. Subsequent eigen-survival analysis shows that the φ ⁽⁴⁰⁾_IL4 signature was robustly associated with overall survival on the 291-sample discovery data set and a 99-sample independent test data set. Regulation of φ ⁽⁴⁰⁾_IL4 by IL4 linked overall survival of ovarian cancer patients with stage 3 disease to macrophage polarization in the tumor environment