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. 2016 Jul;18(4):370-85.
doi: 10.1177/1099800416629209. Epub 2016 Mar 8.

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

Kord M Kober  1 , Laura Dunn  2 , Judy Mastick  1 , Bruce Cooper  1 , Dale Langford  1 , Michelle Melisko  2 , Alan Venook  2 , Lee-May Chen  2 , Fay Wright  3 , Marilyn Hammer  3 , Brian L Schmidt  4 , Jon Levine  2 , Christine Miaskowski  1 , Bradley E Aouizerat  5
Affiliations

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

Kord M Kober et al. Biol Res Nurs. 2016 Jul.

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.

Keywords: breast cancer; cancer; chemotherapy; diurnal variations in fatigue; fatigue; gene expression; inflammation.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Experimental approach and analysis plan. The diagram illustrates the analysis plan for the study, which includes differential expression (blue outline), differential expression profiling (orange outline), pathway analysis (purple outline), transcript origin analysis (red outline), and ProfileChaser (orange outline). Closed boxes denote analysis or software, and open boxes denote data or results. aggregateExprs() = a function contained in the PGSEA R (version 1.44.0) statistical software package; DE = differentially expressed; E.C. genes = essential contributing genes; GAGE = Generally Applicable Gene Set Enrichment; GEO = gene expression omnibus; GO = gene ontogeny; GSE = GEO series; KEGG = Kyoto Encyclopedia of Genes; NK = natural killer; PBMC = peripheral blood mononuclear cell (dendritic); TOA = transcript origin analysis.
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