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Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma
Opioids are commonly prescribed for extended periods of time to patients with advanced clear cell renal cell carcinoma to assist with pain management. Because extended opioid exposure has been shown to affect the vasculature and to be immunosuppressive, we investigated how it may affect the metaboli...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222048/ https://www.ncbi.nlm.nih.gov/pubmed/37240841 http://dx.doi.org/10.3390/life13051196 |
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author | Garige, Mamatha Poncet, Sarah Norris, Alexis Chou, Chao-Kai Wu, Wells W. Shen, Rong-Fong Greenberg, Jacob W. Krane, Louis Spencer Sourbier, Carole |
author_facet | Garige, Mamatha Poncet, Sarah Norris, Alexis Chou, Chao-Kai Wu, Wells W. Shen, Rong-Fong Greenberg, Jacob W. Krane, Louis Spencer Sourbier, Carole |
author_sort | Garige, Mamatha |
collection | PubMed |
description | Opioids are commonly prescribed for extended periods of time to patients with advanced clear cell renal cell carcinoma to assist with pain management. Because extended opioid exposure has been shown to affect the vasculature and to be immunosuppressive, we investigated how it may affect the metabolism and physiology of clear cell renal cell carcinoma. RNA sequencing of a limited number of archived patients’ specimens with extended opioid exposure or non-opioid exposure was performed. Immune infiltration and changes in the microenvironment were evaluated using CIBERSORT. A significant decrease in M1 macrophages and T cells CD4 memory resting immune subsets was observed in opioid-exposed tumors, whereas the changes observed in other immune cells were not statistically significant. Further RNA sequencing data analysis showed that differential expression of KEGG signaling pathways was significant between non-opioid-exposed specimens and opioid-exposed specimens, with a shift from a gene signature consistent with aerobic glycolysis to a gene signature consistent with the TCA cycle, nicotinate metabolism, and the cAMP signaling pathway. Together, these data suggest that extended opioid exposure changes the cellular metabolism and immune homeostasis of ccRCC, which might impact the response to therapy of these patients, especially if the therapy is targeting the microenvironment or metabolism of ccRCC tumors. |
format | Online Article Text |
id | pubmed-10222048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102220482023-05-28 Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma Garige, Mamatha Poncet, Sarah Norris, Alexis Chou, Chao-Kai Wu, Wells W. Shen, Rong-Fong Greenberg, Jacob W. Krane, Louis Spencer Sourbier, Carole Life (Basel) Article Opioids are commonly prescribed for extended periods of time to patients with advanced clear cell renal cell carcinoma to assist with pain management. Because extended opioid exposure has been shown to affect the vasculature and to be immunosuppressive, we investigated how it may affect the metabolism and physiology of clear cell renal cell carcinoma. RNA sequencing of a limited number of archived patients’ specimens with extended opioid exposure or non-opioid exposure was performed. Immune infiltration and changes in the microenvironment were evaluated using CIBERSORT. A significant decrease in M1 macrophages and T cells CD4 memory resting immune subsets was observed in opioid-exposed tumors, whereas the changes observed in other immune cells were not statistically significant. Further RNA sequencing data analysis showed that differential expression of KEGG signaling pathways was significant between non-opioid-exposed specimens and opioid-exposed specimens, with a shift from a gene signature consistent with aerobic glycolysis to a gene signature consistent with the TCA cycle, nicotinate metabolism, and the cAMP signaling pathway. Together, these data suggest that extended opioid exposure changes the cellular metabolism and immune homeostasis of ccRCC, which might impact the response to therapy of these patients, especially if the therapy is targeting the microenvironment or metabolism of ccRCC tumors. MDPI 2023-05-17 /pmc/articles/PMC10222048/ /pubmed/37240841 http://dx.doi.org/10.3390/life13051196 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Garige, Mamatha Poncet, Sarah Norris, Alexis Chou, Chao-Kai Wu, Wells W. Shen, Rong-Fong Greenberg, Jacob W. Krane, Louis Spencer Sourbier, Carole Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma |
title | Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma |
title_full | Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma |
title_fullStr | Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma |
title_full_unstemmed | Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma |
title_short | Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma |
title_sort | extended opioid exposure modulates the molecular metabolism of clear cell renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222048/ https://www.ncbi.nlm.nih.gov/pubmed/37240841 http://dx.doi.org/10.3390/life13051196 |
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