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. 2024 Aug 15;130(16):2834-2847.
doi: 10.1002/cncr.35336. Epub 2024 Apr 27.

Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis

Kate R Oppegaard  1   2 , Samantha J Mayo  3 , Terri S Armstrong  4 , Vasuda Dokiparthi  5 , Michelle Melisko  6 , Jon D Levine  7 , Adam B Olshen  8 , Joaquin A Anguera  9 , Ritu Roy  10 , Steven Paul  1 , Bruce Cooper  1 , Yvette P Conley  11 , Marilyn J Hammer  12 , Christine Miaskowski  13 , Kord M Kober  14
Affiliations

Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis

Kate R Oppegaard et al. Cancer. .

Abstract

Background: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways.

Methods: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database.

Results: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways.

Conclusions: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.

Keywords: anxiety; cancer; chemotherapy‐related cognitive impairment; cognition; gene expression; neurodegeneration; pathway analysis; patient‐reported outcomes.

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