TY - JOUR
T1 - Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy
AU - Flowers, Elena
AU - Miaskowski, Christine
AU - Conley, Yvette
AU - Hammer, Marilyn J.
AU - Levine, Jon
AU - Mastick, Judy
AU - Paul, Steven
AU - Wright, Fay
AU - Kober, Kord
N1 - Publisher Copyright:
© 2017, Springer-Verlag GmbH Germany.
PY - 2018
Y1 - 2018
N2 - Purpose: 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). Methods: 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). Results: 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. Conclusions: 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.
AB - Purpose: 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). Methods: 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). Results: 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. Conclusions: 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.
KW - Cancer
KW - Chemotherapy
KW - Fatigue
KW - Gene expression
KW - Pathway analysis
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U2 - 10.1007/s00520-017-3883-5
DO - 10.1007/s00520-017-3883-5
M3 - Article
C2 - 28944404
AN - SCOPUS:85029897644
SN - 0941-4355
VL - 26
SP - 739
EP - 750
JO - Supportive Care in Cancer
JF - Supportive Care in Cancer
IS - 3
ER -