Differential regulation of NF-kB and IRF target genes as they relate to fatigue in patients with head and neck cancer

• Type of Material: Article
• Authors: Canhua Xiao, Emory University; Jonathan Beitler, Emory University; Kristin Higgins, Emory University; Evanthia C. Wommack, Emory University; Nabil Saba, Emory University; Dong Shin, Emory University; Deborah Bruner, Emory University; Andrew Miller, Emory University; Steve Cole, University of California Los Angeles
• Language: English
• Date: 2018-11-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbi.2018.09.013
• Title of Journal or Parent Work: Brain, Behavior, and Immunity
• ISSN: 0889-1591
• Volume: 74
• Start Page: 291
• End Page: 295
• Grant/Funding Information: The study was supported by NIH/NINR K99/R00NR014587, NIH/NINR R01NR015783, NIH/NCI P30CA138292 and Oncology Nursing Society Foundation.
• Keywords: Science & Technology; EXPRESSION; Neurosciences & Neurology; Immunology; HUMAN-PAPILLOMAVIRUS; INFLAMMATION; SURVIVAL; Neurosciences; Psychiatry; QUALITY-OF-LIFE; RADIOTHERAPY; Life Sciences & Biomedicine; IMMUNITY
• Research Categories: Health Sciences, Immunology; Biology, Neuroscience

Abstract

Previous studies have linked plasma inflammatory markers to elevated fatigue in patients with head and neck cancer (HNC). To identify the molecular mechanisms underlying this association, we conducted promoter-based bioinformatics analyses to determine the relationship between fatigue and specific gene expression profiles associated with inflammation in human papillomavirus (HPV)-related and -unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC without distant metastasis were assessed at baseline (pre-radiotherapy) and one-month post-radiotherapy. Fatigue was measured by the Multidimensional Fatigue Inventory. Genome-wide gene expression profiles were collected from peripheral blood mononuclear cells (PBMC). Promoter-based bioinformatics analyses were employed to identify transcription control pathways underlying transcriptomic correlates of fatigue in the sample as a whole and in HPV-related and HPV-unrelated HNC patients separately. In transcriptome profiling analyses of PBMC from 44 patients, TELiS bioinformatics analyses linked fatigue to increased nuclear factor-kappa B (NF-kB) transcriptional activity and decreased interferon regulatory factor family (IRF) transcription factor activity. Patients with HPV-related HNC showed lower levels of fatigue-related gene expression profile compared to HPV-unrelated HNC. Fatigue in HNC patients undergoing treatment is associated with gene expression profiles consistent with the conserved transcriptional response to adversity (CTRA) characterized by increased proinflammatory and decreased anti-antiviral transcriptional activity. Interestingly, this CTRA response was mitigated in patients with HPV-related HNC and may explain the lower level of fatigue they experience relative to HPV-unrelated HNC.