The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer
Metabolic alterations encountered in tumors are well recognized and considered as a hallmark of cancer. In addition to Warburg Effect, epidemiological and experimental studies support the crucial role of lipid metabolism in colorectal cancer (CRC). The overexpression of four lipid metabolism-related genes (ABCA1, ACSL1, AGPAT1 and SCD genes) has been proposed as prognostic marker of stage II CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic and genomic scenarios of ABCA1, ACSL1, AGPAT1 and SCD genes, we performed a transcriptomic meta-analysis in more than one thousand CRC individuals. Additionally we analyzed their genomic coding sequence in 95 patients, to find variants that could orchestrate CRC prognosis. We found that genetic variant rs3071, located on SCD gene, defines a 9.77% of stage II CRC patients with high risk of death. Moreover, individuals with upregulation of ABCA1 and AGPAT1 expression have an increased risk of CRC recurrence, independently of tumor stage. ABCA1 emerges as one of the main contributors to signature's prognostic effect. Indeed, both high ABCA1 expression and presence of tumoral genetic variants located in ABCA1 coding region, seem to be associated with CRC risk of death. In addition the non-synonymous polymorphism rs2230808, located on ABCA1, is associated with gene expression. Patients carrying at least one copy of minor allele showed higher levels of ABCA1 expression than patients carrying homozygous major allele. This study broaden the prognostic value of ABCA1, ACSL1, AGPAT1 and SCD genes, independently of CRC tumor stage, leading to future precision medicine approaches and "omics"-guided therapies.
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Format: | artículo biblioteca |
Language: | English |
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Impact Journals
2018
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Subjects: | Colorectal cancer, Gene expression profile, Genetic variations, Lipid metabolism, |
Online Access: | http://hdl.handle.net/10261/192914 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100003329 |
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dig-cial-es-10261-1929142019-10-19T01:14:28Z The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer Fernández, Lara P. Ramos, Ricardo Herranz, Jesús Martín-Hernández, Roberto Vargas, Teodoro Mendiola, Marta Guerra, Laura Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana Ministerio de Economía y Competitividad (España) Comunidad de Madrid European Commission Colorectal cancer Gene expression profile Genetic variations Lipid metabolism Metabolic alterations encountered in tumors are well recognized and considered as a hallmark of cancer. In addition to Warburg Effect, epidemiological and experimental studies support the crucial role of lipid metabolism in colorectal cancer (CRC). The overexpression of four lipid metabolism-related genes (ABCA1, ACSL1, AGPAT1 and SCD genes) has been proposed as prognostic marker of stage II CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic and genomic scenarios of ABCA1, ACSL1, AGPAT1 and SCD genes, we performed a transcriptomic meta-analysis in more than one thousand CRC individuals. Additionally we analyzed their genomic coding sequence in 95 patients, to find variants that could orchestrate CRC prognosis. We found that genetic variant rs3071, located on SCD gene, defines a 9.77% of stage II CRC patients with high risk of death. Moreover, individuals with upregulation of ABCA1 and AGPAT1 expression have an increased risk of CRC recurrence, independently of tumor stage. ABCA1 emerges as one of the main contributors to signature's prognostic effect. Indeed, both high ABCA1 expression and presence of tumoral genetic variants located in ABCA1 coding region, seem to be associated with CRC risk of death. In addition the non-synonymous polymorphism rs2230808, located on ABCA1, is associated with gene expression. Patients carrying at least one copy of minor allele showed higher levels of ABCA1 expression than patients carrying homozygous major allele. This study broaden the prognostic value of ABCA1, ACSL1, AGPAT1 and SCD genes, independently of CRC tumor stage, leading to future precision medicine approaches and "omics"-guided therapies. Ministerio de Economía y Competitividad del Gobierno de España (MINECO, Plan Nacional I+D+i AGL2016-76736-C3), Gobierno regional de la Comunidad de Madrid (P2013/ABI-2728, ALIBIRD-CM) and EU Structural Funds. Peer reviewed 2019-10-18T13:01:15Z 2019-10-18T13:01:15Z 2018 artículo http://purl.org/coar/resource_type/c_6501 Oncotarget 9(5): 5919-5930 (2018) http://hdl.handle.net/10261/192914 10.18632/oncotarget.23592 1949-2553 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100003329 29464044 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/AGL2016-76736-C3 S2013/ABI-2728/ALIBIRD-CM Publisher's version https://doi.org/10.18632/oncotarget.23592 Sí open Impact Journals |
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Colorectal cancer Gene expression profile Genetic variations Lipid metabolism Colorectal cancer Gene expression profile Genetic variations Lipid metabolism |
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Colorectal cancer Gene expression profile Genetic variations Lipid metabolism Colorectal cancer Gene expression profile Genetic variations Lipid metabolism Fernández, Lara P. Ramos, Ricardo Herranz, Jesús Martín-Hernández, Roberto Vargas, Teodoro Mendiola, Marta Guerra, Laura Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
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Metabolic alterations encountered in tumors are well recognized and considered as a hallmark of cancer. In addition to Warburg Effect, epidemiological and experimental studies support the crucial role of lipid metabolism in colorectal cancer (CRC). The overexpression of four lipid metabolism-related genes (ABCA1, ACSL1, AGPAT1 and SCD genes) has been proposed as prognostic marker of stage II CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic and genomic scenarios of ABCA1, ACSL1, AGPAT1 and SCD genes, we performed a transcriptomic meta-analysis in more than one thousand CRC individuals. Additionally we analyzed their genomic coding sequence in 95 patients, to find variants that could orchestrate CRC prognosis. We found that genetic variant rs3071, located on SCD gene, defines a 9.77% of stage II CRC patients with high risk of death. Moreover, individuals with upregulation of ABCA1 and AGPAT1 expression have an increased risk of CRC recurrence, independently of tumor stage. ABCA1 emerges as one of the main contributors to signature's prognostic effect. Indeed, both high ABCA1 expression and presence of tumoral genetic variants located in ABCA1 coding region, seem to be associated with CRC risk of death. In addition the non-synonymous polymorphism rs2230808, located on ABCA1, is associated with gene expression. Patients carrying at least one copy of minor allele showed higher levels of ABCA1 expression than patients carrying homozygous major allele. This study broaden the prognostic value of ABCA1, ACSL1, AGPAT1 and SCD genes, independently of CRC tumor stage, leading to future precision medicine approaches and "omics"-guided therapies. |
author2 |
Ministerio de Economía y Competitividad (España) |
author_facet |
Ministerio de Economía y Competitividad (España) Fernández, Lara P. Ramos, Ricardo Herranz, Jesús Martín-Hernández, Roberto Vargas, Teodoro Mendiola, Marta Guerra, Laura Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana |
format |
artículo |
topic_facet |
Colorectal cancer Gene expression profile Genetic variations Lipid metabolism |
author |
Fernández, Lara P. Ramos, Ricardo Herranz, Jesús Martín-Hernández, Roberto Vargas, Teodoro Mendiola, Marta Guerra, Laura Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana |
author_sort |
Fernández, Lara P. |
title |
The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
title_short |
The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
title_full |
The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
title_fullStr |
The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
title_full_unstemmed |
The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
title_sort |
transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer |
publisher |
Impact Journals |
publishDate |
2018 |
url |
http://hdl.handle.net/10261/192914 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100003329 |
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