Nuclear Factor Kappa B Pathway Associated Biomarkers In Aids Defining Malignancies

The nuclear factor kappa B (NF kappa B) pathway is essential for many human cancers. Therapeutics such as bortezomib (Velcade (TM)) that interfere with NF kappa B signaling are of great clinical interest. NF kappa B signaling, however, is multifaceted and variable among tissues, developmental and disease entities. Hence, targeted biomarkers of NF kappa B pathways are of prime importance for clinical research. We developed a novel real-time qPCR-based NF kappa B array. Only mechanistically validated NF kappa B targets were included. We then used random-forest classification to define individual genes and gene combinations within the NF kappa B pathways that define viral lymphoma subclasses as well as Kaposi sarcoma (KS). Few NF kappa B 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 primary effusion lymphoma (PEL); IL1-beta, cyclinD3 and CD48 for KS. We found that IL12, jun-B, msx-1 and thrombospondin 2 were associated with EBV co-infection in PEL. (ii) We defined the NF kappa B signature of EpsteinBarr 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 NF kappa B activity but that this virus also reprograms NF?B signaling toward different targets.