Elena Flowers1,2, Christine Miaskowski3, Yvette Conley4, Marilyn J Hammer5, Jon Levine6, Judy Mastick3, Steven Paul3, Fay Wright7, Kord Kober3,8. 1. Department of Physiological Nursing, University of California, San Francisco, 2 Koret Way, #605L, San Francisco, CA, 94143-0610, USA. elena.flowers@ucsf.edu. 2. Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. elena.flowers@ucsf.edu. 3. Department of Physiological Nursing, University of California, San Francisco, 2 Koret Way, #605L, San Francisco, CA, 94143-0610, USA. 4. School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA. 5. Mount Sinai Medical Center, New York, NY, USA. 6. School of Medicine, University of California, San Francisco, San Francisco, CA, USA. 7. School of Nursing, Yale University, Orange, CT, USA. 8. Institute for Computational Health Sciences, University of California, San Francisco, San Francisco, CA, USA.
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.
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.
Authors: L N Saligan; C P Hsiao; D Wang; X M Wang; L St John; A Kaushal; D Citrin; J J Barb; P J Munson; R A Dionne Journal: Brain Behav Immun Date: 2012-09-26 Impact factor: 7.217
Authors: Sang Mi Kwak; Youn Seon Choi; Ho Min Yoon; Dae Gyun Kim; Seung Hun Song; Young Jae Lee; Chang Hwan Yeom; Su Jin Koh; Jeanno Park; Myung Ah Lee; Sang-Yeon Suh Journal: Palliat Med Date: 2011-08-01 Impact factor: 4.762
Authors: Komal P Singh; Anand Dhruva; Elena Flowers; Steven M Paul; Marilyn J Hammer; Fay Wright; Frances Cartwright; Yvette P Conley; Michelle Melisko; Jon D Levine; Christine Miaskowski; Kord M Kober Journal: J Pain Symptom Manage Date: 2020-01-08 Impact factor: 3.612
Authors: Elena Flowers; Annesa Flentje; Jon Levine; Adam Olshen; Marilyn Hammer; Steven Paul; Yvette Conley; Christine Miaskowski; Kord M Kober Journal: Biol Res Nurs Date: 2019-01-31 Impact factor: 2.522