Supportive Care in Cancer

, Volume 26, Issue 3, pp 739–750 | Cite as

Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy

  • Elena FlowersEmail author
  • Christine Miaskowski
  • Yvette Conley
  • Marilyn J. Hammer
  • Jon Levine
  • Judy Mastick
  • Steven Paul
  • Fay Wright
  • Kord Kober
Original Article



Fatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue in oncology patients may identify new therapeutic targets. The objectives of this study were to evaluate the relationships between gene expression and perturbations in biological pathways and evening fatigue severity in oncology patients who received chemotherapy (CTX).


The Lee Fatigue Scale (LFS) and latent class analysis were used to identify evening fatigue phenotypes. We measured 47,214 ribonucleic acid transcripts from whole blood collected prior to a cycle of CTX. Perturbations in biological pathways associated with differential gene expression were identified from public data sets (i.e., Kyoto Encyclopedia Gene and Genomes, BioCarta).


Patients were classified into Moderate (n = 65, mean LFS score 3.1) or Very High (n = 195, mean LFS score 6.4) evening fatigue groups. Compared to patients with Moderate fatigue, patients with Very High fatigue exhibited differential expression of 29 genes. A number of the perturbed pathways identified validated prior mechanistic hypotheses for fatigue, including alterations in immune function, inflammation, neurotransmission, energy metabolism, and circadian rhythms. Based on our findings, energy metabolism was further divided into alterations in carbohydrate metabolism and skeletal muscle energy. Alterations in renal function-related pathways were identified as a potential new mechanism.


This study identified differential gene expression and perturbed biological pathways that provide new insights into the multiple and likely inter-related mechanisms associated with evening fatigue in oncology patients.


Fatigue Cancer Gene expression Chemotherapy Pathway analysis 



Research reported in this publication was supported by grants from the National Cancer Institute [grant numbers R01CA134900, K05CA168960], the National Center for Advancing Translational Sciences of the National Institutes of Health [grant number KL2TR000143], and the National Institute for Nursing Research [grant number T32NR008346]. Dr. Miaskowski is an American Cancer Society Clinical Research Professor.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

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Supplementary Table 1 (XLSX 93 kb)
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Supplementary Table 2 (XLSX 351 kb)
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Supplementary Table 3 (XLSX 184 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Physiological NursingUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Institute for Human GeneticsUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.School of NursingUniversity of PittsburghPittsburghUSA
  4. 4.Mount Sinai Medical CenterNew YorkUSA
  5. 5.School of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  6. 6.School of NursingYale UniversityOrangeUSA
  7. 7.Institute for Computational Health SciencesUniversity of California, San FranciscoSan FranciscoUSA

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