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3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients
Strong evidence suggests that lipid metabolism (LM) has an essential role in tumor growth to support special energetic and structural requirements of tumor cells. Recently, overexpression of LM-related genes, apolipoproteins related to metabolic syndrome, and ACSL/SCD network involved in fatty acid...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167383/ https://www.ncbi.nlm.nih.gov/pubmed/27992526 http://dx.doi.org/10.1371/journal.pone.0168423 |
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author | Vargas, Teodoro Moreno-Rubio, Juan Herranz, Jesús Cejas, Paloma Molina, Susana Mendiola, Marta Burgos, Emilio Custodio, Ana B. De Miguel, María Martín-Hernández, Roberto Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana |
author_facet | Vargas, Teodoro Moreno-Rubio, Juan Herranz, Jesús Cejas, Paloma Molina, Susana Mendiola, Marta Burgos, Emilio Custodio, Ana B. De Miguel, María Martín-Hernández, Roberto Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana |
author_sort | Vargas, Teodoro |
collection | PubMed |
description | Strong evidence suggests that lipid metabolism (LM) has an essential role in tumor growth to support special energetic and structural requirements of tumor cells. Recently, overexpression of LM-related genes, apolipoproteins related to metabolic syndrome, and ACSL/SCD network involved in fatty acid activation have been proposed as prognostic markers of colon cancer (CC). Furthermore, activation of this latter lipid network has been recently demonstrated to confer invasive and stem cell properties to tumor cells promoting tumor aggressiveness and patient relapse. With the aim of elucidating whether any genetic variation within these genes could influence basal expression levels and consequent susceptibility to relapse, we genotype, in 284 CC patients, 57 polymorphisms located in the 7 genes of these lipid networks previously associated with worse clinical outcome of CC patients (ABCA1, ACSL1, AGPAT1, APOA2, APOC1, APOC2 and SCD), some of them related to CC aggressiveness. After adjusting with clinical confounding factors and multiple comparisons, an association between genotype and disease-free survival (DFS) was shown for rs8086 in 3’-UTR of ACSL1 gene (HR 3.08; 95% CI 1.69–5.63; adjusted p = 0.046). Furthermore, the risk T/T genotype had significantly higher ACSL1 gene expression levels than patients carrying C/T or C/C genotype (means = 5.34; 3.73; 2.37 respectively; p-value (ANOVA) = 0.019), suggesting a functional role of this variant. Thus, we have identified a “risk genotype” of ACSL1 gene that confers constitutive high levels of the enzyme, which is involved in the activation of fatty acids through conversion to acyl-CoA and has been recently related to increased invasiveness of tumor cells. These results suggest that rs8086 of ACSL1 could be a promising prognostic marker in CC patients, reinforcing the relevance of LM in the progression of CC. |
format | Online Article Text |
id | pubmed-5167383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51673832017-01-04 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients Vargas, Teodoro Moreno-Rubio, Juan Herranz, Jesús Cejas, Paloma Molina, Susana Mendiola, Marta Burgos, Emilio Custodio, Ana B. De Miguel, María Martín-Hernández, Roberto Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana PLoS One Research Article Strong evidence suggests that lipid metabolism (LM) has an essential role in tumor growth to support special energetic and structural requirements of tumor cells. Recently, overexpression of LM-related genes, apolipoproteins related to metabolic syndrome, and ACSL/SCD network involved in fatty acid activation have been proposed as prognostic markers of colon cancer (CC). Furthermore, activation of this latter lipid network has been recently demonstrated to confer invasive and stem cell properties to tumor cells promoting tumor aggressiveness and patient relapse. With the aim of elucidating whether any genetic variation within these genes could influence basal expression levels and consequent susceptibility to relapse, we genotype, in 284 CC patients, 57 polymorphisms located in the 7 genes of these lipid networks previously associated with worse clinical outcome of CC patients (ABCA1, ACSL1, AGPAT1, APOA2, APOC1, APOC2 and SCD), some of them related to CC aggressiveness. After adjusting with clinical confounding factors and multiple comparisons, an association between genotype and disease-free survival (DFS) was shown for rs8086 in 3’-UTR of ACSL1 gene (HR 3.08; 95% CI 1.69–5.63; adjusted p = 0.046). Furthermore, the risk T/T genotype had significantly higher ACSL1 gene expression levels than patients carrying C/T or C/C genotype (means = 5.34; 3.73; 2.37 respectively; p-value (ANOVA) = 0.019), suggesting a functional role of this variant. Thus, we have identified a “risk genotype” of ACSL1 gene that confers constitutive high levels of the enzyme, which is involved in the activation of fatty acids through conversion to acyl-CoA and has been recently related to increased invasiveness of tumor cells. These results suggest that rs8086 of ACSL1 could be a promising prognostic marker in CC patients, reinforcing the relevance of LM in the progression of CC. Public Library of Science 2016-12-19 /pmc/articles/PMC5167383/ /pubmed/27992526 http://dx.doi.org/10.1371/journal.pone.0168423 Text en © 2016 Vargas et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Vargas, Teodoro Moreno-Rubio, Juan Herranz, Jesús Cejas, Paloma Molina, Susana Mendiola, Marta Burgos, Emilio Custodio, Ana B. De Miguel, María Martín-Hernández, Roberto Reglero, Guillermo Feliu, Jaime Ramírez de Molina, Ana 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients |
title | 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients |
title_full | 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients |
title_fullStr | 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients |
title_full_unstemmed | 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients |
title_short | 3’UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients |
title_sort | 3’utr polymorphism in acsl1 gene correlates with expression levels and poor clinical outcome in colon cancer patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167383/ https://www.ncbi.nlm.nih.gov/pubmed/27992526 http://dx.doi.org/10.1371/journal.pone.0168423 |
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