PMID- 37629044 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20230829 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 16 DP - 2023 Aug 16 TI - HLA-G Gene Variability Is Associated with Papillary Thyroid Carcinoma Morbidity and the HLA-G Protein Profile. LID - 10.3390/ijms241612858 [doi] LID - 12858 AB - 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. FAU - Bertol, Bruna C AU - Bertol BC AUID- ORCID: 0000-0002-9301-449X AD - Postgraduate Program of Basic and Applied Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. AD - Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. FAU - Debortoli, Guilherme AU - Debortoli G AD - Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON L5L 1C6, Canada. FAU - Dias, Fabricio C AU - Dias FC AD - Division of Clinical Immunology, Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - de Araujo, Jessica N G AU - de Araujo JNG AD - Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil. FAU - Maia, Luana S M AU - Maia LSM AD - Division of Clinical Immunology, Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - de Almeida, Bibiana S AU - de Almeida BS AD - Division of Clinical Immunology, Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - de Figueiredo-Feitosa, Nathalie L AU - de Figueiredo-Feitosa NL AD - Division of Endocrinology and Metabolism, Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - de Freitas, Luiz Carlos C AU - de Freitas LCC AUID- ORCID: 0000-0002-2153-6512 AD - Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - Castelli, Erick C AU - Castelli EC AD - Department of Pathology, School of Medicine, Sao Paulo State University, Botucatu 18618-687, Brazil. FAU - Mendes-Junior, Celso T AU - Mendes-Junior CT AUID- ORCID: 0000-0002-7337-1203 AD - Departamento de Quimica, Faculdade de Filosofia, Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - Silbiger, Vivian N AU - Silbiger VN AUID- ORCID: 0000-0002-9252-0278 AD - Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil. FAU - Maciel, Lea M Z AU - Maciel LMZ AD - Division of Endocrinology and Metabolism, Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. FAU - Donadi, Eduardo A AU - Donadi EA AD - Postgraduate Program of Basic and Applied Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. AD - Division of Clinical Immunology, Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil. LA - eng GR - #2015/26556-0/Sao Paulo Research Foundation/ GR - #457231/2013 and #302060/2019-7/National Council for Scientific and Technological Development/ GR - #88881-068436/2014-1/Programa Nacional de Cooperacao Academica (PROCAD)/ GR - #071/2013/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/ PT - Journal Article DEP - 20230816 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (HLA-G Antigens) RN - 0 (3' Untranslated Regions) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Humans MH - Thyroid Cancer, Papillary/genetics MH - *HLA-G Antigens/genetics MH - 3' Untranslated Regions MH - Morbidity MH - *Thyroid Neoplasms/genetics MH - GTP-Binding Proteins PMC - PMC10454351 OTO - NOTNLM OT - HLA-G OT - haplotypes OT - papillary thyroid carcinoma COIS- The authors declare no conflict of interest. EDAT- 2023/08/26 10:43 MHDA- 2023/08/28 07:16 PMCR- 2023/08/16 CRDT- 2023/08/26 01:16 PHST- 2023/07/16 00:00 [received] PHST- 2023/08/07 00:00 [revised] PHST- 2023/08/15 00:00 [accepted] PHST- 2023/08/28 07:16 [medline] PHST- 2023/08/26 10:43 [pubmed] PHST- 2023/08/26 01:16 [entrez] PHST- 2023/08/16 00:00 [pmc-release] AID - ijms241612858 [pii] AID - ijms-24-12858 [pii] AID - 10.3390/ijms241612858 [doi] PST - epublish SO - Int J Mol Sci. 2023 Aug 16;24(16):12858. doi: 10.3390/ijms241612858.