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

• Published in: Oncotarget Vol. 10; no. 9; pp. 953 - 965
• Main Authors: da Rocha, Natália Pereira, Avvad-Portari, Elyzabeth, Russomano, Fábio, Roma, Eric Henrique, Pinto, Amanda Chaves, Klumb, Evandro, Macedo, Jacyara, Fernandes, Ana Teresa Gomes, da Glória Bonecini-Almeida, Maria
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 29.01.2019
• Subjects: Research Paper; TNFR1 SNPs; cervical lesions; in situ TNFR1; HPV
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.26627

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 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 ( = 179) and healthy volunteers ( = 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, < 0.001) and control ( < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 ( < 0.001), and in ( < 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 /GG and genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression.