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Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with...

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Autores principales: Lucarelli, Giuseppe, Ferro, Matteo, Loizzo, Davide, Bianchi, Cristina, Terracciano, Daniela, Cantiello, Francesco, Bell, Lauren N., Battaglia, Stefano, Porta, Camillo, Gernone, Angela, Perego, Roberto A., Maiorano, Eugenio, de Cobelli, Ottavio, Castellano, Giuseppe, Vincenti, Leonardo, Ditonno, Pasquale, Battaglia, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763669/
https://www.ncbi.nlm.nih.gov/pubmed/33322148
http://dx.doi.org/10.3390/metabo10120509
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author Lucarelli, Giuseppe
Ferro, Matteo
Loizzo, Davide
Bianchi, Cristina
Terracciano, Daniela
Cantiello, Francesco
Bell, Lauren N.
Battaglia, Stefano
Porta, Camillo
Gernone, Angela
Perego, Roberto A.
Maiorano, Eugenio
de Cobelli, Ottavio
Castellano, Giuseppe
Vincenti, Leonardo
Ditonno, Pasquale
Battaglia, Michele
author_facet Lucarelli, Giuseppe
Ferro, Matteo
Loizzo, Davide
Bianchi, Cristina
Terracciano, Daniela
Cantiello, Francesco
Bell, Lauren N.
Battaglia, Stefano
Porta, Camillo
Gernone, Angela
Perego, Roberto A.
Maiorano, Eugenio
de Cobelli, Ottavio
Castellano, Giuseppe
Vincenti, Leonardo
Ditonno, Pasquale
Battaglia, Michele
author_sort Lucarelli, Giuseppe
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.
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spelling pubmed-77636692020-12-27 Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma Lucarelli, Giuseppe Ferro, Matteo Loizzo, Davide Bianchi, Cristina Terracciano, Daniela Cantiello, Francesco Bell, Lauren N. Battaglia, Stefano Porta, Camillo Gernone, Angela Perego, Roberto A. Maiorano, Eugenio de Cobelli, Ottavio Castellano, Giuseppe Vincenti, Leonardo Ditonno, Pasquale Battaglia, Michele Metabolites Article Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance. MDPI 2020-12-13 /pmc/articles/PMC7763669/ /pubmed/33322148 http://dx.doi.org/10.3390/metabo10120509 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lucarelli, Giuseppe
Ferro, Matteo
Loizzo, Davide
Bianchi, Cristina
Terracciano, Daniela
Cantiello, Francesco
Bell, Lauren N.
Battaglia, Stefano
Porta, Camillo
Gernone, Angela
Perego, Roberto A.
Maiorano, Eugenio
de Cobelli, Ottavio
Castellano, Giuseppe
Vincenti, Leonardo
Ditonno, Pasquale
Battaglia, Michele
Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
title Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
title_full Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
title_fullStr Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
title_full_unstemmed Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
title_short Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma
title_sort integration of lipidomics and transcriptomics reveals reprogramming of the lipid metabolism and composition in clear cell renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763669/
https://www.ncbi.nlm.nih.gov/pubmed/33322148
http://dx.doi.org/10.3390/metabo10120509
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