Perturbations in common and distinct inflammatory pathways associated with morning and evening fatigue in outpatients receiving chemo 2022 Kober et al

Sly Saint

Senior Member (Voting Rights)
Abstract
Background
Moderate to severe fatigue occurs in up to 94% of patients with cancer. Recent evidence suggests that morning and evening fatigue are distinct dimensions of physical fatigue. The purposes of this study were to evaluate the transcriptome for common and distinct perturbed inflammatory pathways in patients receiving chemotherapy who reported low versus high levels of morning or low versus high levels of evening cancer-related fatigue.

Methods
Patients completed questionnaires during the week prior to their chemotherapy treatment. Severity of morning and evening fatigue was evaluated using the Lee Fatigue Scale. Gene expression and pathway impact analyses (PIA) were performed in two independent samples using RNA-sequencing (n = 357) and microarray (n = 360). Patterns of interactions between and among these perturbed pathways were evaluated using a knowledge network (KN).

Results
Across the PIA, nine perturbed pathways (FDR < 0.025) were common to both morning and evening fatigue, six were distinct for morning fatigue, and four were distinct for evening fatigue. KN (19 nodes, 39 edges) identified the phosphatidylinositol 3-kinase (PI3K)-Akt pathway node (perturbed in evening fatigue) with the highest betweenness (0.255) and closeness (0.255) centrality indices. The next highest betweenness centrality indices were seen in pathways perturbed in evening fatigue (i.e., nuclear factor kappa B: 0.200, natural killer cell-mediated cytotoxicity: 0.178, mitogen-activated protein kinase: 0.175).

Conclusions
This study describes perturbations in common and distinct inflammatory pathways associated with morning and/or evening fatigue. PI3K-Akt was identified as a bottleneck pathway. The analysis identified potential targets for therapeutic interventions for this common and devastating clinical problem.

https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.5435

While not evaluated in patients undergoing chemotherapy, in a study of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME),40 the C-type lectin receptor signaling pathway was a member of a cluster of pathways enriched for differentially methylated genes associated with CFS severity. CRF and CFS/ME share gene expression patterns at a subset of genes7 and may share underlying mechanisms.41
 
This study describes perturbations in common and distinct inflammatory pathways associated with morning and/or evening fatigue.
They found different types of fatigue? Don't they know that's not supposed to happen (according to those who claim ME fatigue=CF=cancer fatigue=depression fatigue=anything fatigue) :whistle:;)
 
Back
Top