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HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients
HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453083/ https://www.ncbi.nlm.nih.gov/pubmed/34557189 http://dx.doi.org/10.3389/fimmu.2021.698438 |
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author | Vaquero-Yuste, Christian Juarez, Ignacio Molina-Alejandre, Marta Molanes-López, Elisa María López-Nares, Adrián Suárez-Trujillo, Fabio Gutiérrez-Calvo, Alberto López-García, Adela Lasa, Inmaculada Gómez, Remedios Fernández-Cruz, Eduardo Rodrígez-Sainz, Carmen Arnaiz-Villena, Antonio Martín-Villa, José Manuel |
author_facet | Vaquero-Yuste, Christian Juarez, Ignacio Molina-Alejandre, Marta Molanes-López, Elisa María López-Nares, Adrián Suárez-Trujillo, Fabio Gutiérrez-Calvo, Alberto López-García, Adela Lasa, Inmaculada Gómez, Remedios Fernández-Cruz, Eduardo Rodrígez-Sainz, Carmen Arnaiz-Villena, Antonio Martín-Villa, José Manuel |
author_sort | Vaquero-Yuste, Christian |
collection | PubMed |
description | HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches. |
format | Online Article Text |
id | pubmed-8453083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84530832021-09-22 HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients Vaquero-Yuste, Christian Juarez, Ignacio Molina-Alejandre, Marta Molanes-López, Elisa María López-Nares, Adrián Suárez-Trujillo, Fabio Gutiérrez-Calvo, Alberto López-García, Adela Lasa, Inmaculada Gómez, Remedios Fernández-Cruz, Eduardo Rodrígez-Sainz, Carmen Arnaiz-Villena, Antonio Martín-Villa, José Manuel Front Immunol Immunology HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches. Frontiers Media S.A. 2021-09-07 /pmc/articles/PMC8453083/ /pubmed/34557189 http://dx.doi.org/10.3389/fimmu.2021.698438 Text en Copyright © 2021 Vaquero-Yuste, Juarez, Molina-Alejandre, Molanes-López, López-Nares, Suárez-Trujillo, Gutiérrez-Calvo, López-García, Lasa, Gómez, Fernández-Cruz, Rodrígez-Sainz, Arnaiz-Villena and Martín-Villa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Vaquero-Yuste, Christian Juarez, Ignacio Molina-Alejandre, Marta Molanes-López, Elisa María López-Nares, Adrián Suárez-Trujillo, Fabio Gutiérrez-Calvo, Alberto López-García, Adela Lasa, Inmaculada Gómez, Remedios Fernández-Cruz, Eduardo Rodrígez-Sainz, Carmen Arnaiz-Villena, Antonio Martín-Villa, José Manuel HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients |
title | HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients |
title_full | HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients |
title_fullStr | HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients |
title_full_unstemmed | HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients |
title_short | HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients |
title_sort | hla-g 3’utr polymorphisms are linked to susceptibility and survival in spanish gastric adenocarcinoma patients |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453083/ https://www.ncbi.nlm.nih.gov/pubmed/34557189 http://dx.doi.org/10.3389/fimmu.2021.698438 |
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