The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer
Entity
UAM. Departamento de Ecología; UAM. Departamento de Medicina; UAM. Departamento de Química Física AplicadaPublisher
Impact JournalsDate
2018-01-01Citation
10.18632/oncotarget.23592
Oncotarget 9.5 (2018): 5919-5930
ISSN
1949-2553DOI
10.18632/oncotarget.23592Funded by
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 FundsProject
Gobierno de España. AGL2016-76736-C3; Comunidad de Madrid. P2013/ABI-2728/ALIBIRD-CMEditor's Version
https://doi.org/10.18632/oncotarget.23592Subjects
Colorectal cancer; Gene expression profile; Genetic variations; Lipid metabolism; Prognosis; Ciencia y Tecnología de Alimentos; MedicinaRights
© 2018 Fernández et al.Abstract
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
Files in this item
Google Scholar:Fernández, Lara P.
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Ramos-Ruiz, Ricardo
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Herranz Barrera, Jesús
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Martín-Hernández, Roberto
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Vargas, Teodoro
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Mendiola, Marta
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Guerra, Laura
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Reglero Rada, Guillermo J.
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Feliú Batlle, Jaime
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Ramírez de Molina, Ana
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