Genomic Profile of Fatigued Men Receiving Localized Radiation Therapy

Abstract

Fatigue intensification was associated with MS4A1 downregulation, suggesting that fatigue during EBRT may be related to impairment in B-cell immune response. The 42 differentially expressed fatigue-related genes are associated with glutathione biosynthesis, γ-glutamyl cycle, and antigen presentation pathways.

Genomic mechanisms of fatigue in survivors of colorectal cancer

“…Instead, the results herein implicated lymphoid lineage cells, particularly B lymphocytes and CD8‐positive T lymphocytes. Previous studies also have implicated B cells in the leukocyte transcriptomic correlates of fatigue . Consistent with that observation, SNCA is known to influence B‐cell homeostasis and differentiation in addition to its better known role in neuronal integrity as the non‐A β component of Alzheimer disease amyloid …”

“…Analyses estimating the magnitude of association between leukocyte gene expression and MFSI‐SF scores identified 280 gene transcripts demonstrating a ≥1.5‐fold difference in expression over the 4‐SD range of normal variation in MFSI‐SF scores after controlling for age, sex, BMI, smoking history, and alcohol use (155 of which were upregulated and 120 of which were downregulated). Upregulated genes (see Supporting Table ) included several transcripts associated with fatigue, such as the amyloid subunit SNCA and multiple hemoglobin subunits ( HBA1, HBA2, HBB , and HBG2 ) . Other upregulated transcripts included indicators of immunologic activation (human leukocyte antigen [ HLA ] ‐B, HLA‐H , and LTB ) and related transcriptional regulators ( EGR1, ETS1, ATF4 , high mobility group box 1 [ HMGB1 ], HMGB2, JUND, KLF2 , and EIF1 ), as well as several small nucleolar RNAs (small nucleolar RNA, H/ACA box 3B [ SNORA45 ], SNORA63, SNORD3A, SNORD3C, SNORD3D, SNORD13 , and SNORD89 ).…”

“…These include the upregulation of genes coding for α‐synuclein ( SNCA ) and hemoglobin subunits ( HB family genes) . B and T lymphocytes have been implicated as cellular mediators of these dynamics . However, to the best of our knowledge, the majority of these findings remain provisional because they have not been replicated in independent samples or in different types of cancer.…”

The Etiology and management of radiotherapy-induced fatigue

“…We recently proposed the biological underpinnings of RIF, based on the biomarkers and biological pathways we observed from our investigations, which indicated that cancer and cancer treatment induce a cascade of biological changes causing RIF [33–37]. These biomarkers and biological pathways include alpha-synuclein [34], neurotrophic factors ( BDNF, GDNF , and SNAPIN ) [35], para-inflammatory bystander markers (the interferon alpha-inducible protein 27, IFI27 ) [36], and immunespecific response markers (e.g.…”

“…These biomarkers and biological pathways include alpha-synuclein [34], neurotrophic factors ( BDNF, GDNF , and SNAPIN ) [35], para-inflammatory bystander markers (the interferon alpha-inducible protein 27, IFI27 ) [36], and immunespecific response markers (e.g. MS4A1 ) [37], mitochondrial associated genes ( BCL2L1, FIS2, BCS1L , and SCL25A37 ) as well as RIF-associated biological pathways (glutathione biosynthesis, γ-glutamyl cycle, and antigen presentation pathways) [37]. …”