دورية أكاديمية
Systematic Evaluation of HLA-G 3'Untranslated Region Variants in Locally Advanced, Non-Metastatic Breast Cancer Patients: UTR-1, 2 or UTR-4 are Predictors for Therapy and Disease Outcome
| العنوان: | Systematic Evaluation of HLA-G 3'Untranslated Region Variants in Locally Advanced, Non-Metastatic Breast Cancer Patients: UTR-1, 2 or UTR-4 are Predictors for Therapy and Disease Outcome |
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| المؤلفون: | Rebmann, Vera, Schwich, Esther, Michita, Rafael Tomoya, Grüntkemeier, Lisa, Bittner, Ann-Kathrin, Rohn, Hana, Horn, Peter A., Hoffmann, Oliver, Kimmig, Rainer, Kasimir-Bauer, Sabine |
| سنة النشر: | 2022 |
| المجموعة: | University of Duisburg-Essen: DuEPublico (Duisburg Essen Publications online) |
| مصطلحات موضوعية: | ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Transfusionsmedizin, Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Infektiologie, Humans, Breast Neoplasms, Genetic Predisposition to Disease, 3' Untranslated Regions, Prognosis, Tumor Burden, Genotype, Haplotypes, Polymorphism, Single Nucleotide, Alleles, Adolescent, Adult, Aged, 80 and over, Middle Aged, Female, Genetic Variation, Young Adult, Genetic Association Studies, HLA-G Antigens, Biomarkers, Tumor, Breast cancer, HLA-G, Hla-G 3’Utr Polymorphism |
| الوصف: | Despite major improvements in diagnostics and therapy in early as well as in locally advanced breast cancer (LABC), metastatic relapse occurs in about 20% of patients, often explained by early micro-metastatic spread into bone marrow by disseminated tumor cells (DTC). Although neoadjuvant chemotherapy (NACT) has been a successful tool to improve overall survival (OS), there is growing evidence that various environmental factors like the non-classical human leukocyte antigen-G (HLA-G) promotes cancer invasiveness and metastatic progression. HLA-G expression is associated with regulatory elements targeting certain single-nucleotide polymorphisms (SNP) in the HLA-G 3' untranslated region (UTR), which arrange as haplotypes. Here, we systematically evaluated the impact of HLA-G 3'UTR polymorphisms on disease status, on the presence of DTC, on soluble HLA-G levels, and on therapy and disease outcome in non-metastatic LABC patients. Although haplotype frequencies were similar in patients (n = 142) and controls (n = 204), univariate analysis revealed that the UTR-7 haplotype was related to patients with low tumor burden, whereas UTR-4 was associated with tumor sizes >T1. Furthermore, UTR-4 was associated with the presence of DTC, but UTR-3 and UTR-7 were related to absence of DTC. Additionally, increased levels of soluble HLA-G molecules were found in patients carrying UTR-7. Regarding therapy and disease outcome, univariate and multivariate analysis highlighted UTR-1 or UTR-2 as a prognostic parameter indicative for a beneficial course of disease in terms of complete response towards NACT or progression-free survival (PFS). At variance, UTR-4 was an independent risk factor for a reduced OS besides already known parameters. Taken into account the most common HLA-G 3'UTR haplotypes (UTR-1-UTR-7, UTR-18), deduction of the UTR-1/2/4 haplotypes to specific SNPs revealed that the +3003C variant, unique for UTR-4, seemed to favor a detrimental disease outcome, while the +3187G and +3196G variants, unique for UTR-1 or ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.3389/fimmu.2021.817132Test; https://nbn-resolving.org/urn:nbn:de:hbz:465-20220804-092141-3Test; https://duepublico2.uni-due.de/receive/duepublico_mods_00076402Test; https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00076141/fimmu_2022-12-817132.pdfTest |
| DOI: | 10.3389/fimmu.2021.817132 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2021.817132Test https://nbn-resolving.org/urn:nbn:de:hbz:465-20220804-092141-3Test https://duepublico2.uni-due.de/receive/duepublico_mods_00076402Test https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00076141/fimmu_2022-12-817132.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D56062A8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2021.817132 |
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