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Genomic mechanisms of fatigue in colorectal cancer survivors
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March 26 2018
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Source: Cancer. 124(12):2637-2644
[PDF-480.37 KB]
Details:
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Alternative Title:Cancer
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Personal Author:
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Description:Objective
Many cancer survivors experience fatigue as a nagging symptom lasting years after treatment. To learn of the relevant biological pathways involved in fatigue among cancer survivors, we tested for an association between fatigue levels and leukocyte gene expression profiles and determined the specific mediating immune cell types.
Methods
A sample of N=89 Hispanic/Latino adults diagnosed with colorectal cancer aged 60.5 years, 2.9 years since diagnosis, and 62% male provided blood for transcriptome profiling and completed a validated measure of fatigue (Multidimensional Fatigue Inventory-Short Form). We applied genome-wide transcriptional profiling of leukocyte RNA to identify gene expression activity associated with fatigue, tested for activity of specific transcription factors involved in previously established markers of inflammation and immunologic activation, and identified the specific cell types mediating these transcriptional alterations.
Results
In analyses adjusting for demographic and behavioral health risk factors, results linked fatigue to increased activation of B lymphocytes and CD8+ T cells, as well as several transcription factors involved in immune activation (NF-κB, STAT, and CREB). Results also replicated several specific genomic effects previously observed in fatigued cancer survivors, including up-regulated expression of alpha-synuclein (SNCA) and hemoglobin subunits (HBA and HBB).
Conclusions
Cancer survivors’ heightened fatigue levels may be partially explained by activation of specific immune cell subsets, providing a potential molecular biomarker for clinical interventions targeting the remediation of fatigue.
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Pubmed ID:29579369
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Pubmed Central ID:PMC5990448
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Funding:
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Volume:124
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Issue:12
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