Nuclear factor kappa B pathway associated biomarkers in AIDS defining malignancies

Juan Carlos Ramos, Sang Hoon Sin, Michelle R. Staudt, Debasmita Roy, Wolfgang Vahrson, Bruce J. Dezube, William Harrington, Dirk P. Dittmer

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2728-2733
Number of pages6
JournalInternational Journal of Cancer
Volume130
Issue number11
DOIs
StatePublished - Jun 1 2012

Keywords

  • ATL
  • Burkitt lymphoma
  • EBV
  • Kaposi sarcoma
  • KSHV
  • random forest
  • real-time qPCR
  • tree

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Ramos, J. C., Sin, S. H., Staudt, M. R., Roy, D., Vahrson, W., Dezube, B. J., Harrington, W., & Dittmer, D. P. (2012). Nuclear factor kappa B pathway associated biomarkers in AIDS defining malignancies. International Journal of Cancer, 130(11), 2728-2733. https://doi.org/10.1002/ijc.26302