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01.03.2018 | Original Article | Ausgabe 3/2018

Supportive Care in Cancer 3/2018

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

Supportive Care in Cancer > Ausgabe 3/2018
Elena Flowers, Christine Miaskowski, Yvette Conley, Marilyn J. Hammer, Jon Levine, Judy Mastick, Steven Paul, Fay Wright, Kord Kober
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00520-017-3883-5) contains supplementary material, which is available to authorized users.



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.

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