HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival

Abstract Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is r...

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Main Authors: Christian Vaquero-Yuste, Ignacio Juarez, Marta Molina-Alejandre, Elisa María Molanes-López, Alberto Gutiérrez-Calvo, Adela López-García, Inmaculada Lasa, Remedios Gómez, Antonio Arnaiz-Villena, Jose Manuel Martín-Villa
Format: Article
Language:English
Published: Springer 2024-11-01
Series:Cancer Immunology, Immunotherapy
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Online Access:https://doi.org/10.1007/s00262-024-03771-w
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author Christian Vaquero-Yuste
Ignacio Juarez
Marta Molina-Alejandre
Elisa María Molanes-López
Alberto Gutiérrez-Calvo
Adela López-García
Inmaculada Lasa
Remedios Gómez
Antonio Arnaiz-Villena
Jose Manuel Martín-Villa
author_facet Christian Vaquero-Yuste
Ignacio Juarez
Marta Molina-Alejandre
Elisa María Molanes-López
Alberto Gutiérrez-Calvo
Adela López-García
Inmaculada Lasa
Remedios Gómez
Antonio Arnaiz-Villena
Jose Manuel Martín-Villa
author_sort Christian Vaquero-Yuste
collection DOAJ
description Abstract Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3’ untranslated region (3’UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3’UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan–Meier curves and multivariate Cox regression models. High-expressor HLA-G 3’UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14 bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer.
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spelling doaj-art-ff35db722aef44888cbab112f50e9e652025-02-02T12:26:33ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-017411610.1007/s00262-024-03771-wHLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survivalChristian Vaquero-Yuste0Ignacio Juarez1Marta Molina-Alejandre2Elisa María Molanes-López3Alberto Gutiérrez-Calvo4Adela López-García5Inmaculada Lasa6Remedios Gómez7Antonio Arnaiz-Villena8Jose Manuel Martín-Villa9Departamento de Inmunología, Oftalmología y ORL, Facultad de Medicina, Universidad Complutense de MadridDepartamento de Inmunología, Oftalmología y ORL, Facultad de Medicina, Universidad Complutense de MadridDepartamento de Inmunología, Oftalmología y ORL, Facultad de Medicina, Universidad Complutense de MadridDepartamento de Estadística e Investigación Operativa, Facultad de Medicina, Universidad Complutense de MadridServicio de Cirugía General y Aparato Digestivo, Hospital Universitario Príncipe de AsturiasServicio de Cirugía General y Aparato Digestivo, Hospital Universitario Príncipe de AsturiasServicio de Cirugía General y Aparato Digestivo, Hospital Universitario Príncipe de AsturiasServicio de Cirugía General y Aparato Digestivo, Hospital Universitario Príncipe de AsturiasDepartamento de Inmunología, Oftalmología y ORL, Facultad de Medicina, Universidad Complutense de MadridDepartamento de Inmunología, Oftalmología y ORL, Facultad de Medicina, Universidad Complutense de MadridAbstract Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3’ untranslated region (3’UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3’UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan–Meier curves and multivariate Cox regression models. High-expressor HLA-G 3’UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14 bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer.https://doi.org/10.1007/s00262-024-03771-wHLA-G antigensStomach neoplasmPrognosisHaplotypesClinical relevanceTumor escape
spellingShingle Christian Vaquero-Yuste
Ignacio Juarez
Marta Molina-Alejandre
Elisa María Molanes-López
Alberto Gutiérrez-Calvo
Adela López-García
Inmaculada Lasa
Remedios Gómez
Antonio Arnaiz-Villena
Jose Manuel Martín-Villa
HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival
Cancer Immunology, Immunotherapy
HLA-G antigens
Stomach neoplasm
Prognosis
Haplotypes
Clinical relevance
Tumor escape
title HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival
title_full HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival
title_fullStr HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival
title_full_unstemmed HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival
title_short HLA-G high-expressor 3’UTR markers are linked to gastric cancer development and survival
title_sort hla g high expressor 3 utr markers are linked to gastric cancer development and survival
topic HLA-G antigens
Stomach neoplasm
Prognosis
Haplotypes
Clinical relevance
Tumor escape
url https://doi.org/10.1007/s00262-024-03771-w
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