Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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
_version_ 1784570216155447296
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
work_keys_str_mv AT vaqueroyustechristian hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT juarezignacio hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT molinaalejandremarta hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT molaneslopezelisamaria hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT lopeznaresadrian hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT suareztrujillofabio hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT gutierrezcalvoalberto hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT lopezgarciaadela hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT lasainmaculada hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT gomezremedios hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT fernandezcruzeduardo hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT rodrigezsainzcarmen hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT arnaizvillenaantonio hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients
AT martinvillajosemanuel hlag3utrpolymorphismsarelinkedtosusceptibilityandsurvivalinspanishgastricadenocarcinomapatients