A Pilot Study Using a Multistaged Integrated Analysis of Gene Expression and Methylation to Evaluate Mechanisms for Evening Fatigue in Women Who Received Chemotherapy for Breast Cancer

Elena Flowers, Annesa Flentje, Jon Levine, Adam Olshen, Marilyn Hammer, Steven Paul, Yvette Conley, Christine Miaskowski, Kord M. Kober

Research output: Contribution to journalArticle

Abstract

Context: Fatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue may identify new therapeutic targets. Objective: The objective of this pilot study was to evaluate the relationships between gene expression and methylation status and evening fatigue severity in women with breast cancer who received chemotherapy. Methods: Latent class analysis (LCA) was used to identify evening fatigue phenotypes. In this analysis, the lowest (i.e., moderate, n = 7) and highest (i.e., very high, n = 29) fatigue-severity classes identified using LCA were analyzed via two stages. First, a total of 32,609 transcripts from whole blood were evaluated for differences in expression levels between the classes. Next, 637 methylation sites located within the putative transcription factor binding sites for those genes demonstrating differential expression were evaluated for differential methylation state between the classes. Results: A total of 89 transcripts in 75 unique genes were differentially expressed between the moderate (the lowest fatigue-severity class identified) and very high evening fatigue classes. In addition, 23 differentially methylated probes and three differentially methylated regions were found between the moderate and very high evening fatigue classes. Conclusions: Using a multistaged integrated analysis of gene expression and methylation, differential methylation was identified in the regulatory regions of genes associated with previously hypothesized mechanisms for fatigue, including inflammation, immune function, neurotransmission, circadian rhythm, skeletal muscle energy, carbohydrate metabolism, and renal function as well as core biological processes including gene transcription and the cell-cycle regulation.

Original languageEnglish (US)
Pages (from-to)142-156
Number of pages15
JournalBiological Research for Nursing
Volume21
Issue number2
DOIs
StatePublished - Mar 1 2019

Fingerprint

Methylation
Fatigue
Breast Neoplasms
Gene Expression
Drug Therapy
Biological Phenomena
cdc Genes
Nucleic Acid Regulatory Sequences
Carbohydrate Metabolism
Regulator Genes
Circadian Rhythm
Synaptic Transmission
Energy Metabolism
Genes
Skeletal Muscle
Transcription Factors
Binding Sites
Inflammation
Phenotype
Kidney

Keywords

  • breast cancer
  • chemotherapy
  • fatigue
  • gene expression
  • integrated genomic analysis
  • methylation

ASJC Scopus subject areas

  • Research and Theory

Cite this

A Pilot Study Using a Multistaged Integrated Analysis of Gene Expression and Methylation to Evaluate Mechanisms for Evening Fatigue in Women Who Received Chemotherapy for Breast Cancer. / Flowers, Elena; Flentje, Annesa; Levine, Jon; Olshen, Adam; Hammer, Marilyn; Paul, Steven; Conley, Yvette; Miaskowski, Christine; Kober, Kord M.

In: Biological Research for Nursing, Vol. 21, No. 2, 01.03.2019, p. 142-156.

Research output: Contribution to journalArticle

Flowers, Elena ; Flentje, Annesa ; Levine, Jon ; Olshen, Adam ; Hammer, Marilyn ; Paul, Steven ; Conley, Yvette ; Miaskowski, Christine ; Kober, Kord M. / A Pilot Study Using a Multistaged Integrated Analysis of Gene Expression and Methylation to Evaluate Mechanisms for Evening Fatigue in Women Who Received Chemotherapy for Breast Cancer. In: Biological Research for Nursing. 2019 ; Vol. 21, No. 2. pp. 142-156.
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