Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/32208
Title: TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression
Authors: Rocha, Natália Pereira da
Avvad-Portari, Elyzabeth
Russomano, Fábio
Roma, Eric Henrique
Pinto, Amanda Chaves
Klumb, Evandro
Macedo, Jacyara
Fernandes, Ana Teresa Gomes
Bonecini-Almeida, Maria da Glória
Affilliation: Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Anatomia Patológica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
State University of Rio de Janeiro. Department of Biochemistry. Rio de Janeiro, RJ, Brazil.
State University of Rio de Janeiro. Department of Rheumatology. Rio de Janeiro, RJ, Brazil.
State University of Rio de Janeiro. Department of Biochemistry. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Abstract: TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated TNFR1 rs767455 andrs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development. SIL patients (n = 179) and healthy volunteers (n = 227) were enrolled for TNFR1 genotyping analysis by PCR-RFLP in blood samples and TNFR1 protein expression in cervical tissue by immunohistochemistry. No statistical differences regard genotypes and allelic frequencies for both polymorphisms were observed. Cervical TNFR1-expressing cells were rare in epithelium and basal layer regardless the groups. However, a progressive increase in infiltrating cells was observed in the stromal area, mainly in high SIL (HSIL) group compared to low SIL (LSIL, p <0.001) and control (p < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 rs767455AG/GG (p < 0.001), and in rs2234649AA (p < 0.001) genotypes carries in HSIL subgroup. These data indicated that TNFR1-expression is abrogated in cervical epithelium, where HPV-induced pre-malignant lesion occurs, increasing its frequency in inflammatory cells in stroma, and is genetically controlled by TNFR1 rs767455AG/GG and rs234649AA genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression.
Keywords: HPV
Cervical lesions
In situ TNFR1
TNFR1 SNPs
Issue Date: 2019
Publisher: Impact Journals
Citation: ROCHA, Natália Pereira da et al. TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression. Oncotarget, v. 10, n. 9, p. 953-965, 2019.
Copyright: open access
Appears in Collections:IFF - Artigos de Periódicos
INI - Artigos de Periódicos

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