title: Gene Expression Profiling of Evening Fatigue in Women Undergoing Chemotherapy for Breast Cancer.
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.
authors.affiliation: School of Nursing, University of California, San Francisco, CA, USA.
authors.forename: Kord M
authors.initials: KM
authors.lastname: Kober
authors.affiliation: School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Dunn
authors.affiliation: School of Nursing, University of California, San Francisco, CA, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Mastick
authors.affiliation: School of Nursing, University of California, San Francisco, CA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Cooper
authors.affiliation: School of Nursing, University of California, San Francisco, CA, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Langford
authors.affiliation: School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Melisko
authors.affiliation: School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Venook
authors.affiliation: School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Lee-May
authors.initials: LM
authors.lastname: Chen
authors.affiliation: College of Nursing, New York University, New York, NY, USA.
authors.forename: Fay
authors.initials: F
authors.lastname: Wright
authors.affiliation: College of Nursing, New York University, New York, NY, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Hammer
authors.affiliation: Department of Oral and Maxillofacial Surgery, New York University, New York, NY, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Schmidt
authors.affiliation: School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Levine
authors.affiliation: School of Nursing, University of California, San Francisco, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Miaskowski
authors.affiliation: School of Nursing, University of California, San Francisco, CA, USA Institute for Human Genetics, University of California, San Francisco, CA, USA bea4@nyu.edu.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002940:Circadian Rhythm / Q000235:genetics*; D005221:Fatigue / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D010507:Periodicity
chemical_list: D000970:Antineoplastic Agents
keywords: breast cancer; cancer; chemotherapy; diurnal variations in fatigue; fatigue; gene expression; inflammation