HLA-G Gene Variability Is Associated with Papillary Thyroid Carcinoma Morbidity and the HLA-G Protein Profile.

Autor: Bertol BC; Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada., Debortoli G; Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON L5L 1C6, Canada., Dias FC; Division of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., de Araújo JNG; Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil., Maia LSM; Division of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., de Almeida BS; Division of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., de Figueiredo-Feitosa NL; Division of Endocrinology and Metabolism, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., de Freitas LCC; Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Castelli EC; Department of Pathology, School of Medicine, São Paulo State University, Botucatu 18618-687, Brazil., Mendes-Junior CT; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil., Silbiger VN; Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil., Maciel LMZ; Division of Endocrinology and Metabolism, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Donadi EA; Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.; Division of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Aug 16; Vol. 24 (16). Date of Electronic Publication: 2023 Aug 16.
DOI: 10.3390/ijms241612858
Abstrakt: Human leukocyte antigen (HLA)-G is an immune checkpoint molecule that is highly expressed in papillary thyroid carcinoma (PTC). The HLA-G gene presents several functional polymorphisms distributed across the coding and regulatory regions (5'URR: 5' upstream regulatory region and 3'UTR: 3' untranslated region) and some of them may impact HLA-G expression and human malignancy. To understand the contribution of the HLA-G genetic background in PTC, we studied the HLA-G gene variability in PTC patients in association with tumor morbidity, HLA-G tissue expression, and plasma soluble (sHLA-G) levels. We evaluated 185 PTC patients and 154 healthy controls. Polymorphic sites defining coding, regulatory and extended haplotypes were characterized by sequencing analyses. HLA-G tissue expression and plasma soluble HLA-G levels were evaluated by immunohistochemistry and ELISA, respectively. Compared to the controls, the G 0104a (5'URR) G* 01:04:04 (coding) UTR-03 (3'UTR) extended haplotype was underrepresented in the PTC patients, while G 0104a (5'URR) G* 01:04:01 (coding) UTR-03 (3'UTR) was less frequent in patients with metastatic and multifocal tumors. Decreased HLA-G tissue expression and undetectable plasma sHLA-G were associated with the G 010102a (5'URR) G* 01:01:02:01 (coding) UTR-02 (3'UTR) extended haplotype. We concluded that the HLA-G variability was associated with PTC development and morbidity, as well as the magnitude of the encoded protein expression at local and systemic levels.
Databáze: MEDLINE
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