Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Garige, Mamatha, Poncet, Sarah, Norris, Alexis, Chou, Chao-Kai, Wu, Wells W., Shen, Rong-Fong, Greenberg, Jacob W., Krane, Louis Spencer, Sourbier, Carole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785049602844524544
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
work_keys_str_mv AT garigemamatha extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT poncetsarah extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT norrisalexis extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT chouchaokai extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT wuwellsw extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT shenrongfong extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT greenbergjacobw extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT kranelouisspencer extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma
AT sourbiercarole extendedopioidexposuremodulatesthemolecularmetabolismofclearcellrenalcellcarcinoma