Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea.

CONTEXT: Despite current advances in antiemetic treatments, approximately 50% of oncology patients experience chemotherapy-induced nausea (CIN).

OBJECTIVES: The purpose of this study was to evaluate for differentially expressed genes and perturbed pathways associated with the gut-brain axis (GBA) across two independent samples of oncology patients who did and did not experience CIN.

METHODS: Oncology patients (n=735) completed study questionnaires in the week prior to their second or third cycle of chemotherapy (CTX). CIN occurrence was assessed using the Memorial Symptom Assessment Scale. Gene expression analyses were performed in two independent samples using RNA-sequencing (sample 1, n=357) and microarray (sample 2, n=352) methodologies. Fisher's combined probability method was used to determine genes that were differentially expressed and pathways that were perturbed between the two nausea groups across both samples.

RESULTS: CIN was reported by 63.6% of the patients in sample 1 and by 48.9% of the patients in sample 2. Across the two samples, 703 genes were differentially expressed and 37 pathways were found to be perturbed between the two CIN groups. We identified nine perturbed pathways that are involved in mechanisms associated with alterations in the GBA (i.e., mucosal inflammation, disruption of gut microbiome).

CONCLUSIONS: Persistent CIN remains a significant clinical problem. Our study is the first to identify novel GBA-related pathways associated with the occurrence of CIN. Our findings warrant confirmation and suggest directions for future clinical studies to decrease CIN occurrence.