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

Kate Oppegaard, Carolyn S. Harris, Joosun Shin, Steven M. Paul, Bruce A. Cooper, Alexandre Chan, Joaquin A. Anguera, Jon Levine, Yvette Conley, Marilyn Hammer, Christine A. Miaskowski, Raymond J. Chan, Kord M. Kober

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number155653
Number of pages11
JournalCytokine
Volume148
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Cancer-related cognitive impairment
  • Chemotherapy
  • Gene expression
  • IL-17 signaling pathway
  • MAPK signaling pathway

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