HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

Simple item page
dc.contributor.authorVaquero Yuste, Christian
dc.contributor.authorJuárez Martín-Delgado, Ignacio
dc.contributor.authorMolina Alejandre, Marta
dc.contributor.authorMolanes López, Elisa María
dc.contributor.authorLópez Nares, Adrián
dc.contributor.authorSuárez Trujillo, Fabio
dc.contributor.authorGutiérrez Calvo, Alberto
dc.contributor.authorFernández-Cruz Pérez, Eduardo
dc.contributor.authorRodríguez Sainz, Carmen
dc.contributor.authorMartín Villa, José Manuel
dc.contributor.authorArnaiz Villena, Antonio
dc.date.accessioned2024-01-31T11:28:43Z
dc.date.available2024-01-31T11:28:43Z
dc.date.issued2021
dc.description.abstractHLA-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.
dc.description.departmentDepto. de Inmunología, Oftalmología y ORL
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.statuspub
dc.identifier.citationVaquero-Yuste C, Juarez I, Molina-Alejandre M, Molanes-López EM, López-Nares A, Suárez-Trujillo F, Gutiérrez-Calvo A, López-García A, Lasa I, Gómez R, Fernández-Cruz E, Rodrígez-Sainz C, Arnaiz-Villena A, Martín-Villa JM. HLA-G 3'UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients. Front Immunol. 2021 Sep 7;12:698438. doi: 10.3389/fimmu.2021.698438
dc.identifier.doi10.3389/fimmu.2021.698438
dc.identifier.issn1664-3224
dc.identifier.officialurlhttps://doi.org/10.3389/fimmu.2021.698438
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/34557189/
dc.identifier.relatedurlhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.698438/full
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97030
dc.journal.titleFrontiers in Immunology
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.projectIDPI18/0062
dc.relation.projectIDPI18/0072
dc.relation.projectIDFEDER
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu612.017
dc.subject.keyword+3142 C/G
dc.subject.keyword14bp INS/DEL
dc.subject.keywordHLA-G
dc.subject.keywordAdenocarcinoma
dc.subject.keywordCancer
dc.subject.keywordGastric cancer
dc.subject.keywordImmunoediting
dc.subject.keywordImmunotherapy
dc.subject.ucmInmunología
dc.subject.unesco2412 Inmunología
dc.titleHLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number12
dspace.entity.typePublication
relation.isAuthorOfPublication0894d58b-fe71-42aa-ad0a-19305823daa1
relation.isAuthorOfPublication29ce7a95-21d0-40ec-9fbe-c1062ff6d0a2
relation.isAuthorOfPublicationbc1e21d4-e192-43a6-8a94-63a74d8f378f
relation.isAuthorOfPublicationd6c35711-8ed5-412f-8345-8b8e3869353a
relation.isAuthorOfPublicationd2f85bbc-31c7-4587-8da2-1dc2a3e22d74
relation.isAuthorOfPublication.latestForDiscovery0894d58b-fe71-42aa-ad0a-19305823daa1
Download
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Gastric_Adenocarcinoma_Patients-.pdf
Size:
1.54 MB
Format:
Adobe Portable Document Format
downoload Download
Collections
Artículos