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

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.

SUBMITTER: Flowers E

PROVIDER: S-EPMC5786467 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Flowers Elena E Miaskowski Christine C Conley Yvette Y Hammer Marilyn J MJ Levine Jon J Mastick Judy J Paul Steven S Wright Fay F Kober Kord K

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20170925 3

<h4>Purpose</h4>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).<h4>Methods</h4>The Lee Fatigue Scale (LFS) and latent class analysis were ...[more]

PMID: 28944404

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Project description:Fatigue, a highly prevalent and distressing symptom during chemotherapy (CTX), demonstrates diurnal and interindividual variability in severity. Little is known about the associations between variations in genes involved in inflammatory processes and morning and evening fatigue severity during CTX. The purposes of this study, in a sample of oncology patients (N=543) with breast, gastrointestinal (GI), gynecological (GYN), or lung cancer who received two cycles of CTX, were to determine whether variations in genes involved in inflammatory processes were associated with inter-individual variability in initial levels as well as in the trajectories of morning and evening fatigue. Patients completed the Lee Fatigue Scale to determine morning and evening fatigue severity a total of six times over two cycles of CTX. Using a whole exome array, 309 single nucleotide polymorphisms SNPs among the 64 candidate genes that passed all quality control filters were evaluated using hierarchical linear modeling (HLM). Based on the results of the HLM analyses, the final SNPs were evaluated for their potential impact on protein function using two bioinformational tools. The following inflammatory pathways were represented: chemokines (3 genes); cytokines (12 genes); inflammasome (11 genes); Janus kinase/signal transducers and activators of transcription (JAK/STAT, 10 genes); mitogen-activated protein kinase/jun amino-terminal kinases (MAPK/JNK, 3 genes); nuclear factor-kappa beta (NFkB, 18 genes); and NFkB and MAP/JNK (7 genes). After controlling for self-reported and genomic estimates of race and ethnicity, polymorphisms in six genes from the cytokine (2 genes); inflammasome (2 genes); and NFkB (2 genes) pathways were associated with both morning and evening fatigue. Polymorphisms in six genes from the inflammasome (1 gene); JAK/STAT (1 gene); and NFkB (4 genes) pathways were associated with only morning fatigue. Polymorphisms in three genes from the inflammasome (2 genes) and the NFkB (1 gene) pathways were associated with only evening fatigue. Taken together, these findings add to the growing body of evidence that suggests that morning and evening fatigue are distinct symptoms.

Dataset Information

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

Publications

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

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