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. 2021 Dec:148:155653.
doi: 10.1016/j.cyto.2021.155653. Epub 2021 Aug 10.

Cancer-related cognitive impairment is associated with perturbations in inflammatory pathways

Kate Oppegaard  1 , Carolyn S Harris  2 , Joosun Shin  3 , Steven M Paul  4 , Bruce A Cooper  5 , Alexandre Chan  6 , Joaquin A Anguera  7 , Jon Levine  8 , Yvette Conley  9 , Marilyn Hammer  10 , Christine A Miaskowski  11 , Raymond J Chan  12 , Kord M Kober  13
Affiliations

Cancer-related cognitive impairment is associated with perturbations in inflammatory pathways

Kate Oppegaard et al. Cytokine. 2021 Dec.

Abstract

Cancer-related cognitive impairment (CRCI) is a significant problem for patients receiving chemotherapy. While a growing amount of pre-clinical and clinical evidence suggests that inflammatory mechanisms underlie CRCI, no clinical studies have evaluated for associations between CRCI and changes in gene expression. Therefore, the purpose of this study was to evaluate for differentially expressed genes and perturbed inflammatory pathways across two independent samples of patients with cancer who did and did not report CRCI. The Attentional Function Index (AFI) was the self-report measure used to assess CRCI. AFI scores of <5 and of >7.5 indicate low versus high levels of cognitive function, respectively. Of the 185 patients in Sample 1, 49.2% had an AFI score of <5 and 50.8% had an AFI score of >7.5. Of the 158 patients in Sample 2, 50.6% had an AFI score of <5 and 49.4% had an AFI score of >7.5. Data from 182 patients in Sample 1 were analyzed using RNA-seq. Data from 158 patients in Sample 2 were analyzed using microarray. Twelve KEGG signaling pathways were significantly perturbed between the AFI groups, five of which were signaling pathways related to inflammatory mechanisms (e.g., cytokine-cytokine receptor interaction, tumor necrosis factor signaling). This study is the first to describe perturbations in inflammatory pathways associated with CRCI. Findings highlight the role of cytokines both in terms of cytokine-specific pathways, as well as pathways involved in cytokine production and cytokine activation. These findings have the potential to identify new targets for therapeutics and lead to the development of interventions to improve cognition in patients with cancer.

Keywords: Cancer-related cognitive impairment; Chemotherapy; Gene expression; IL-17 signaling pathway; MAPK signaling pathway.

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Conflict of interest statement

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
A network representation of the KEGG tumor necrosis factor (TNF) signaling pathway (hsa04668). Genes and their products are depicted as nodes shaped as ellipses. Nodes with missing data are shaded gray. The log2 fold change of differential gene expression between patients with low Attentional Function Index (AFI) as compared to high AFI scores are included in a pie representation for each ellipse. Sample 1 values are on the left side of the pie and Sample 2 are on the right. Edges are depicted by the interaction between the nodes.
See this image and copyright information in PMC

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References

    1. Horowitz TS, Treviño M, Gooch IM, Duffy KA. Understanding the Profile of Cancer-Related Cognitive Impairments: A Critique of Meta-Analyses. JNCI : Journal of the National Cancer Institute. 2019;111(10):1009–1015. - PMC - PubMed
    1. Ren X, Boriero D, Chaiswing L, Bondada S, St. Clair DK, Butterfield DA. Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2019;1865(6):1088–1097. - PMC - PubMed
    1. Von Ah D, Storey S, Crouch A. Relationship between self-reported cognitive function and work-related outcomes in breast cancer survivors. J Cancer Surviv. 2018;12(2):246–255. - PubMed
    1. Von Ah D, Storey S, Tallman E, Nielsen A, Johns SA, Pressler S. Cancer, cognitive impairment, and work-related outcomes: An integrative review. Oncology Nursing Forum. 2016;43(5):602–616. - PubMed
    1. Myers JS. Cancer- and chemotherapy-related cognitive changes: the patient experience. Seminars in Oncology Nursing. 2013;29(4):300–307. - PubMed

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