Perturbed Inflammatory, Proliferation, Regulatory, And Neurodegeneration Signaling Pathways Are Associated With Trait Anxiety In Cancer Survivors.

Introduction: Trait anxiety is a prevalent yet under-studied symptom in cancer survivors, linked to stress and reduced quality of life. The purpose of this study was to evaluate perturbed biological pathways associated with trait anxiety severity in both cancer survivors and the general population to understand overlap between these cohorts. Methods: Participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective longitudinal study, were used in this analysis (PHD #39341). Complete gene expression data were available for 1,093 participants at the first visit, and trait anxiety was assessed using ten questions from the Spielberger Trait Anxiety Scale. Participants were split into low (< 3rd quartile) and high (≥ 3rd quartile) trait anxiety groups. Analyses were performed separately for cancer survivors and the general population. Differential gene expression was evaluated between low and high trait anxiety groups, adjusting for covariates. Pathway impact analysis was used to identify perturbed pathways (FDR < 0.025). Results: Forty-two pathways were perturbed in the cancer survivor cohort (n = 74, low anxiety = 63, high anxiety = 11). Eighty pathways were perturbed in the non-cancer cohort (n = 222, low anxiety = 181, high anxiety = 41). Thirty-six pathways overlapped between cohorts, including inflammatory, proliferation, neurodegeneration, and regulatory pathways. Six pathways were unique to cancer survivors. Inflammatory pathways emerged as a shared mechanism across both cohorts. Conclusions: This study is the first to evaluate transcriptomic perturbations in pathways associated with trait anxiety in cancer survivors and a matched non-cancer cohort. Findings identify shared and distinct mechanisms underlying trait anxiety in cancer survivors, suggesting potential targets for future interventions.