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- Title
HLA-G Gene Variability Is Associated with Papillary Thyroid Carcinoma Morbidity and the HLA-G Protein Profile.
- Authors
Bertol, Bruna C.; Debortoli, Guilherme; Dias, Fabrício C.; de Araújo, Jéssica N. G.; Maia, Luana S. M.; de Almeida, Bibiana S.; de Figueiredo-Feitosa, Nathalie L.; de Freitas, Luiz Carlos C.; Castelli, Erick C.; Mendes-Junior, Celso T.; Silbiger, Vivian N.; Maciel, Léa M. Z.; Donadi, Eduardo A.
- Abstract
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 G0104a(5′URR)G*01:04:04(coding)UTR-03(3'UTR) extended haplotype was underrepresented in the PTC patients, while G0104a(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 G010102a(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.
- Subjects
HISTOCOMPATIBILITY class I antigens; PAPILLARY carcinoma; THYROID cancer; HLA histocompatibility antigens; IMMUNE checkpoint proteins; BRAF genes
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 16, p12858
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241612858