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

Elena Flowers, Christine Miaskowski, Yvette Conley, Marilyn Hammer, Jon Levine, Judy Mastick, Steven Paul, Fay Wright, Kord Kober

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)739-750
Number of pages11
JournalSupportive Care in Cancer
DOIs
StatePublished - 2018

Fingerprint

Fatigue
Gene Expression
Drug Therapy
Energy Metabolism
Encyclopedias
Carbohydrate Metabolism
Circadian Rhythm
Synaptic Transmission
Skeletal Muscle
Genome
RNA
Inflammation
Phenotype
Kidney

Keywords

  • Cancer
  • Chemotherapy
  • Fatigue
  • Gene expression
  • Pathway analysis

ASJC Scopus subject areas

  • Oncology

Cite this

Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy. / Flowers, Elena; Miaskowski, Christine; Conley, Yvette; Hammer, Marilyn; Levine, Jon; Mastick, Judy; Paul, Steven; Wright, Fay; Kober, Kord.

In: Supportive Care in Cancer, 2018, p. 739-750.

Research output: Contribution to journalArticle

Flowers, Elena ; Miaskowski, Christine ; Conley, Yvette ; Hammer, Marilyn ; Levine, Jon ; Mastick, Judy ; Paul, Steven ; Wright, Fay ; Kober, Kord. / Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy. In: Supportive Care in Cancer. 2018 ; pp. 739-750.
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abstract = "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.",
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AU - Flowers, Elena

AU - Miaskowski, Christine

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AU - Hammer, Marilyn

AU - Levine, Jon

AU - Mastick, Judy

AU - Paul, Steven

AU - Wright, Fay

AU - Kober, Kord

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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.

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