The large majority of cell signaling pathways were central immune system responses and were associated with CD signaling (e.g., CD72 → AP-1 expression targets, CD8 → ATF/CREB/CREBBP expression targets, and CD8 → NF-κB expression targets) as well as interleukins (e.g., IL-1A expression targets, IL-1B expression targets, IL-6 expression targets, IL-6/JAK/STAT3 signaling in cholesteatoma, IL16 → AP-1 expression targets), and Toll receptors (e.g., TLR1/2/6 → NF-κB signaling, TLR4 → AP-1 expression targets, and Toll-like receptors acting through MYD88-TIRAP signaling). The gene discussed is CREB1; the disease is cholesteatoma.