Gene Expression Profiling of Evening Fatigue in Women Undergoing Chemotherapy for Breast Cancer

Kord M. Kober, Laura Dunn, Judy Mastick, Bruce Cooper, Dale Langford, Michelle Melisko, Alan Venook, Lee May Chen, Fay Wright, Marilyn Hammer, Brian L. Schmidt, Jon Levine, Christine Miaskowski, Bradley E. Aouizerat

Research output: Contribution to journalArticle

Abstract

Moderate-to-severe fatigue occurs in up to 94% of oncology patients undergoing active treatment. Current interventions for fatigue are not efficacious. A major impediment to the development of effective treatments is a lack of understanding of the fundamental mechanisms underlying fatigue. In the current study, differences in phenotypic characteristics and gene expression profiles were evaluated in a sample of breast cancer patients undergoing chemotherapy (CTX) who reported low (n = 19) and high (n = 25) levels of evening fatigue. Compared to the low group, patients in the high evening fatigue group reported lower functional status scores, higher comorbidity scores, and fewer prior cancer treatments. One gene was identified as upregulated and 11 as downregulated in the high evening fatigue group. Gene set analysis found 24 downregulated and 94 simultaneously up- and downregulated pathways between the two fatigue groups. Transcript origin analysis found that differential expression (DE) originated primarily from monocytes and dendritic cell types. Query of public data sources found 18 gene expression experiments with similar DE profiles. Our analyses revealed that inflammation, neurotransmitter regulation, and energy metabolism are likely mechanisms associated with evening fatigue severity; that CTX may contribute to fatigue seen in oncology patients; and that the patterns of gene expression may be shared with other models of fatigue (e.g., physical exercise and pathogen-induced sickness behavior). These results suggest that the mechanisms that underlie fatigue in oncology patients are multifactorial.

Original languageEnglish (US)
Pages (from-to)370-385
Number of pages16
JournalBiological Research for Nursing
Volume18
Issue number4
DOIs
StatePublished - Jul 1 2016

Keywords

  • breast cancer
  • cancer
  • chemotherapy
  • diurnal variations in fatigue
  • fatigue
  • gene expression
  • inflammation

ASJC Scopus subject areas

  • Research and Theory

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  • Cite this

    Kober, K. M., Dunn, L., Mastick, J., Cooper, B., Langford, D., Melisko, M., Venook, A., Chen, L. M., Wright, F., Hammer, M., Schmidt, B. L., Levine, J., Miaskowski, C., & Aouizerat, B. E. (2016). Gene Expression Profiling of Evening Fatigue in Women Undergoing Chemotherapy for Breast Cancer. Biological Research for Nursing, 18(4), 370-385. https://doi.org/10.1177/1099800416629209