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

Komal P Singh, Anand Dhruva, Elena Flowers, Steven M Paul, Marilyn J Hammer, Fay Wright, Frances Cartwright, Yvette P Conley, Michelle Melisko, Jon D Levine, Christine Miaskowski, Kord M Kober

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalJournal of Pain and Symptom Management
DOIs
StateE-pub ahead of print - Jan 7 2020

Fingerprint

Nausea
Gene Expression
Drug Therapy
Brain
Genes
RNA Sequence Analysis
Antiemetics
Symptom Assessment
Inflammation

Cite this

Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea. / Singh, Komal P; Dhruva, Anand; Flowers, Elena; Paul, Steven M; Hammer, Marilyn J; Wright, Fay; Cartwright, Frances; Conley, Yvette P; Melisko, Michelle; Levine, Jon D; Miaskowski, Christine; Kober, Kord M.

In: Journal of Pain and Symptom Management, 07.01.2020.

Research output: Contribution to journalArticle

Singh, Komal P ; Dhruva, Anand ; Flowers, Elena ; Paul, Steven M ; Hammer, Marilyn J ; Wright, Fay ; Cartwright, Frances ; Conley, Yvette P ; Melisko, Michelle ; Levine, Jon D ; Miaskowski, Christine ; Kober, Kord M. / Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea. In: Journal of Pain and Symptom Management. 2020.
@article{bcbdb94b633a49bca9462a5141c00789,
title = "Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea",
abstract = "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.",
author = "Singh, {Komal P} and Anand Dhruva and Elena Flowers and Paul, {Steven M} and Hammer, {Marilyn J} and Fay Wright and Frances Cartwright and Conley, {Yvette P} and Michelle Melisko and Levine, {Jon D} and Christine Miaskowski and Kober, {Kord M}",
note = "Copyright {\circledC} 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = "1",
day = "7",
doi = "10.1016/j.jpainsymman.2019.12.352",
language = "English (US)",
journal = "Journal of Pain and Symptom Management",
issn = "0885-3924",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea

AU - Singh, Komal P

AU - Dhruva, Anand

AU - Flowers, Elena

AU - Paul, Steven M

AU - Hammer, Marilyn J

AU - Wright, Fay

AU - Cartwright, Frances

AU - Conley, Yvette P

AU - Melisko, Michelle

AU - Levine, Jon D

AU - Miaskowski, Christine

AU - Kober, Kord M

N1 - Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

PY - 2020/1/7

Y1 - 2020/1/7

N2 - 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.

AB - 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.

U2 - 10.1016/j.jpainsymman.2019.12.352

DO - 10.1016/j.jpainsymman.2019.12.352

M3 - Article

C2 - 31923555

JO - Journal of Pain and Symptom Management

JF - Journal of Pain and Symptom Management

SN - 0885-3924

ER -