Nuclear factor kappa B pathway associated biomarkers in AIDS defining malignancies. Academic Article uri icon

Overview

MeSH

  • Gene Expression Profiling
  • Humans
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Tumor Markers, Biological

MeSH Major

  • Lymphoma, AIDS-Related
  • NF-kappa B
  • Sarcoma, Kaposi
  • Signal Transduction

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. Copyright © 2011 UICC.

publication date

  • June 1, 2012

has subject area

  • Gene Expression Profiling
  • Humans
  • Lymphoma, AIDS-Related
  • NF-kappa B
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Sarcoma, Kaposi
  • Signal Transduction
  • Tumor Markers, Biological

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3265660

Digital Object Identifier (DOI)

  • 10.1002/ijc.26302

PubMed ID

  • 21792887

Additional Document Info

start page

  • 2728

end page

  • 2733

volume

  • 130

number

  • 11