Abstract
The Nuclear Factor kappa B (NFkB) pathway is essential for many human cancers. Therapeutics such as bortezomib (Velcade
™
), which interfere with nuclear factor NF-kappa-B(NFkB)signaling are of great clinical interest. NFkB signaling, however, is multifaceted and variable among tissues, developmental, and disease entities. Hence, targeted biomarkers of NFkB pathways are of prime importance for clinical research. We developed a novel real-time qPCR-based NFkB array. Only mechanistically validated NFkB targets were included. We then used random-forest classification to define individual genes and gene combinations within the NFkB pathways that define viral lymphoma subclasses as well as Kaposi sarcoma (KS). Few NFkB targets emerged that were universally present in all tumor types tested, underscoring the need for additional tumor-type specific biomarker discovery. (i) We uncovered tissue of origin-specific tumor markers, specifically CD69, CSF-1, and complement factor B (C1QBP)for PEL; IL1-beta, cyclinD3 and CD48for KS. We found that IL12, jun-B, msx-1 and thrombospondin 2 were associated with EBV co-infection in PEL. (ii) We defined the NFkB signature of Epstein-Barr virus (EBV)positive AIDS-associated Burkitt lymphoma(BL). This signature identified CCR5 as the key marker. (iii) This signature differed from EBV negative BL consistent with the idea that EBV not only activates NFkB activity but that this virus also reprograms NFkB signaling towards different targets.
