TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression.

Autor:	da Rocha NP; Laboratory of Immunology and Immunogenetics in Infectious Diseases, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Avvad-Portari E; Department of Pathologic Anatomy, Fernandes Figueira Woman, Child and Adolescent National Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Russomano F; Women's Health Care Area, Fernandes Figueira Woman, Child and Adolescent National Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Roma EH; Laboratory of Immunology and Immunogenetics in Infectious Diseases, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Pinto AC; Department of Biochemistry, State University of Rio de Janeiro, Rio de Janeiro, Brazil., Klumb E; Department of Rheumatology, State University of Rio de Janeiro, Rio de Janeiro, Brazil., Macedo J; Department of Biochemistry, State University of Rio de Janeiro, Rio de Janeiro, Brazil., Fernandes ATG; Laboratory of Immunology and Immunogenetics in Infectious Diseases, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., da Glória Bonecini-Almeida M; Laboratory of Immunology and Immunogenetics in Infectious Diseases, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2019 Jan 29; Vol. 10 (9), pp. 953-965. Date of Electronic Publication: 2019 Jan 29 (Print Publication: 2019).
DOI:	10.18632/oncotarget.26627
Abstrakt:	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 and rs2234649 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. Competing Interests: CONFLICTS OF INTEREST None of the authors have conflicts of interest to declare related to this work.
Databáze:	MEDLINE
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