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Nuclear factor kappa B pathway associated biomarkers in AIDS defining malignancies
Author(s) -
Ramos JuanCarlos,
Sin SangHoon,
Staudt Michelle R.,
Roy Debasmita,
Vahrson Wolfgang,
Dezube Bruce J.,
Harrington William,
Dittmer Dirk P.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26302
Subject(s) - primary effusion lymphoma , lymphoma , cancer research , biology , gene signature , nfkb1 , nf κb , biomarker , immunology , transcription factor , gene , inflammation , gene expression , genetics
The nuclear factor kappa B (NFκB) pathway is essential for many human cancers. Therapeutics such as bortezomib (Velcade™) that interfere with NFκB signaling are of great clinical interest. NFκB signaling, however, is multifaceted and variable among tissues, developmental and disease entities. Hence, targeted biomarkers of NFκB pathways are of prime importance for clinical research. We developed a novel real‐time qPCR‐based NFκB array. Only mechanistically validated NFκB targets were included. We then used random‐forest classification to define individual genes and gene combinations within the NFκB pathways that define viral lymphoma subclasses as well as Kaposi sarcoma (KS). Few NFκB 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 NFκB 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 NFκB activity but that this virus also reprograms NFκB signaling toward different targets.