Komal Singh1, Huangshen Cao2, Christine Miaskowski3, Yvette P Conley4, Marilyn Hammer5, Fay Wright6, Jon D Levine7, Kord M Kober3. 1. Edson College of Nursing and Health Innovation, 7864Arizona State University, Phoenix, AZ, USA. 2. Biodesign Center for Fundamental and Applied Microbiomics, 7864Arizona State University, Tempe, AZ, USA. 3. School of Nursing, 8785University of California, San Francisco, CA, USA. 4. School of Nursing, 6614University of Pittsburgh, Pittsburgh, PA, USA. 5. The Phyllis F. Cantor Center for Research in Nursing and Patient Care Services, Dana Farber Cancer Institute, Boston, MA, USA. 6. Rory Myers College of Nursing, New York University, NY, USA. 7. School of Medicine, 8785University of California, San Francisco, CA, USA.
Abstract
BACKGROUND: While vomiting is well controlled with current antiemetic regimens, unrelieved chemotherapy-induced nausea (CIN) is a significant clinical problem. Perturbations in endocytotic and apoptotic pathways in the gut can influence the functioning of the microbiome-gut-brain-axis and the occurrence of gastrointestinal (GI) symptoms. However, limited information is available on the mechanisms that underlie unrelieved CIN. OBJECTIVES: The purpose of this study was to evaluate for perturbed biological pathways associated with endocytosis and apoptosis in oncology patients who did (n = 353) and did not (n = 275) report CIN prior to their second or third cycle of chemotherapy (CTX). METHODS: Oncology patients (n = 735) completed study questionnaires in the week prior to their second or third cycle of CTX. CIN occurrence was evaluated using the Memorial Symptom Assessment Scale. Pathway impact analyses (PIA) were performed in 2 independent samples using RNA-sequencing (sample 1, n = 334) and microarray (sample 2, n = 294) methodologies. Fisher's combined probability method was used to identify signaling pathways related to endocytotic and apoptotic mechanisms that were significantly perturbed between the 2 nausea groups across both samples. RESULTS: CIN was reported by 63.6% of the patients in sample 1 and 48.9% of the patients in sample 2. Across the 2 samples, PIA identified 4 perturbed pathways that are involved in endocytosis (i.e., endocytosis, regulation of actin cytoskeleton) and apoptosis (i.e., apoptosis, PI3K/Akt signaling). CONCLUSIONS: Our findings suggest that CTX-induced inflammation of the GI mucosa, that results in the initiation of endocytotic and apoptotic processes in the gut, is associated with the occurrence of CIN.
BACKGROUND: While vomiting is well controlled with current antiemetic regimens, unrelieved chemotherapy-induced nausea (CIN) is a significant clinical problem. Perturbations in endocytotic and apoptotic pathways in the gut can influence the functioning of the microbiome-gut-brain-axis and the occurrence of gastrointestinal (GI) symptoms. However, limited information is available on the mechanisms that underlie unrelieved CIN. OBJECTIVES: The purpose of this study was to evaluate for perturbed biological pathways associated with endocytosis and apoptosis in oncology patients who did (n = 353) and did not (n = 275) report CIN prior to their second or third cycle of chemotherapy (CTX). METHODS: Oncology patients (n = 735) completed study questionnaires in the week prior to their second or third cycle of CTX. CIN occurrence was evaluated using the Memorial Symptom Assessment Scale. Pathway impact analyses (PIA) were performed in 2 independent samples using RNA-sequencing (sample 1, n = 334) and microarray (sample 2, n = 294) methodologies. Fisher's combined probability method was used to identify signaling pathways related to endocytotic and apoptotic mechanisms that were significantly perturbed between the 2 nausea groups across both samples. RESULTS: CIN was reported by 63.6% of the patients in sample 1 and 48.9% of the patients in sample 2. Across the 2 samples, PIA identified 4 perturbed pathways that are involved in endocytosis (i.e., endocytosis, regulation of actin cytoskeleton) and apoptosis (i.e., apoptosis, PI3K/Akt signaling). CONCLUSIONS: Our findings suggest that CTX-induced inflammation of the GI mucosa, that results in the initiation of endocytotic and apoptotic processes in the gut, is associated with the occurrence of CIN.
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