HLA-G 14 bp In/Del and +3142 C/G genotypes are differentially expressed between patients with grade IV gliomas and controls

Aim: Human Leukocyte Antigen-G (HLA-G) is a non-classical class I molecule that is involved in maternal-fetal immunotolerance. In cancer, this molecule contributes to the tumor escape. The aim of this study was to evaluate the 14 bp In/Del and +3142 C > G polymorphisms of the HLA-G 3′ UTR and its...

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Published in:	International journal of neuroscience Vol. 131; no. 4; pp. 327 - 335
Main Authors:	de Magalhães, Kênia Cristina S.F., Silva, Karla R., Gomes, Nathália A., Sadissou, Ibrahim, Carvalho, Gérvasio T., Buzellin, Marcelo A., Tafuri, Luciene S., Nunes, Cristiana B., Nunes, Maurício B., Donadi, Eduardo A., da Silva, Istéfani Luciene, Simões, Renata T.
Format:	Journal Article
Language:	English
Published:	England Taylor & Francis 03-04-2021
Subjects:	3′ UTR Brain tumors GBM HLA-G polymorphism plasma expression HLA-G polymorphism GBM plasma expression 3′ UTR Brain tumors
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Summary:	Aim: Human Leukocyte Antigen-G (HLA-G) is a non-classical class I molecule that is involved in maternal-fetal immunotolerance. In cancer, this molecule contributes to the tumor escape. The aim of this study was to evaluate the 14 bp In/Del and +3142 C > G polymorphisms of the HLA-G 3′ UTR and its relation with plasma and tissue HLA-G expression in patients with grade IV (high-grade) and grade I/II (low-grade) gliomas and controls. Patients and methods: Peripheral blood and tumor biopsies were collected from 85 patients with gliomas and blood samples from 94 controls. Polymorphisms were analyzed from blood DNA. Soluble HLA-G (sHLA-G) was measured by ELISA in plasma of the subjects and the tissue expression by immunohistochemistry on patient's tissue. Results: Higher levels of sHLA-G were observed in grade IV gliomas patients than in controls (p < 0.0001). In grade IV patients, the heterozygous 14pb In/Del, +3142 C/G genotypes and Del/C*In/G haplotype were associated with higher sHLA-G levels (p < 0.0001) when compared with controls. GBM patients were stratified into high and low sHLA-G expression and an association was found between +3142 C allele and high sHLA-G plasmatic levels (p = 0.0095). Tissue HLA-G immunolabel was higher in high-grade than low-grade gliomas (p = 0.0033). Conclusion: This was the first study evaluating HLA-G 3′ UTR polymorphisms and expression in patients with gliomas. The 14 bp In/Del and +3142 C/G genotypes and haplotypes showed high influence over sHLA-G expression, suggesting a heterozygous advantage in the tumor context and may contribute to a worse prognosis in glioma patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0020-7454 1563-5279 1543-5245
DOI:	10.1080/00207454.2020.1744593