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

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Bertol, Bruna C. ; Debortoli, Guilherme ; Dias, Fabricio C. ; de Araujo, Jessica 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, Lea M. Z. ; Donadi, Eduardo A.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 16, p. 17-pg., 2023-08-01.

Resumo

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 30 UTR: 30 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. (AU)

• Processo FAPESP: 15/26556-0 - Associação dos genes HLA-G, BRAF e TERT com a malignidade do carcinoma papilífero de tireoide
• Beneficiário: Bruna Cristina Bertol
• Modalidade de apoio: Bolsas no Brasil - Doutorado