Dataset Information

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

ABSTRACT: TNF-? 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-? 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.

SUBMITTER: da Rocha NP

PROVIDER: S-EPMC6398171 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

da Rocha Natália Pereira NP Avvad-Portari Elyzabeth E Russomano Fábio F Roma Eric Henrique EH Pinto Amanda Chaves AC Klumb Evandro E Macedo Jacyara J Fernandes Ana Teresa Gomes ATG da Glória Bonecini-Almeida Maria M

Oncotarget 20190129 9

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 = 2 ...[more]

PMID: 30847024

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Project description:As the fourth most common gynecological cancer, cervical cancer has resulted in more than 300,000 deaths worldwide in 2020. The expression of the human papillomavirus (HPV) oncogenes E6 and E7 is significantly involved in the initiation and progression of cervical neoplasia. Additionally, the composition of the vaginal microbiome was also closely associated with the ability of HPV to induce cervical cancer. However, the relationship between the expression of HPV E6/E7 oncogene and the composition of the vaginal microbiome has not been clearly explored. In our present study, to investigate the relationship between the HPV E6/E7 oncogene and vaginal microbiome, cervical swabs from 115 patients were collected, and their vaginal microbiomes were analyzed by using metagenomics sequencing. Along with the progression of cervical lesions, the diversity of cervical flora increased gradually, and the abundance of Lactobacillus decreased. Compared with the HPV group, the prevalence of HPV E6/E7 and oncogene expression level were significantly upregulated in cervical intraepithelial neoplasia (CIN) and cervical cancer (CC) groups. Additionally, a positive correlation between the expression of the HPV oncogene and the genera Sneathia, Salmonella, Leptotrichia, Pseudomonas, and Roseovarius in the HPV group was observed. In the CIN group, the enrichment of the genera Sneathia and Megasphaera was weakly linked with HPV oncogene overexpression. In the CC group, a strong association between the overabundance of the genera Peptostreptococcus and Enterococcus and the high expression of HPV oncogene was also found. The increased diversity of the vaginal microbiota and the decreased Lactobacillus abundance were significantly associated with the severity of cervical disease, and the expression of the HPV oncogene could also be regulated by certain pathogens in different stages of cervical lesions. IMPORTANCE The main findings of this study were that we clarified the associations of the different bacterial species with the expression of human papillomavirus (HPV) oncogenes at different stages of cervical cancer. Along with the severity of cervical lesions, the abundance of the genus and species of Lactobacillus obviously declined, while the aerobic and anaerobic bacteria, as well as the prevalence and expression of HPV E6/E7 oncogene, were increased dramatically.

Project description:BackgroundCervical cancer is a preventable disease if treated early, but remains the second leading cause of cancer-related mortality among women in low and middle-income countries. Data on epidemiology and risk factors in these settings are scarce. This study aimed to assess the prevalence of pre-cancerous cervical lesions and risk factors in Tigray region, Ethiopia.MethodsA community-based, cross-sectional study was used and 900 participants were 30 recruited using multistage sampling and finally data from 883 were collected using an interviewer administered questionnaire and screening with visual inspection with ascetic acid. Data were collected using an interviewer administered questionnaire and screening with visual inspection with acetic acid from March 2016 to June 2017. Multinomial logistic regression analysis was conducted to estimate predictors.ResultsSeventy-nine (8.95%) women were positive for pre-cancer lesion and 35 (3.96%) were suspicious for cervical cancer. We used relative risk ratio (rrr) to estimate the strength of association. Divorced or widowed women had 2.5 and 4.7 times more risk of being positive and suspicious respectively, compared to single women (rrr = 2.5, 95% CI [1.13, 5.52]); (rrr = 4.69, 95% CI [1.00, 21.84]). The risk of having a suspicious result was 68% lower for women with primary education compared to those with no formal education (rrr = 0.32, 95% CI [1.00, 21.84]). History of sexually transmitted infection was associated with positive pre cancer lesion (rrr = 1.91, 95% CI [1.11, 3.27]) whereas, being farmer (rrr = 4.83, 95% CI [1.44, 16.13]), merchant (rrr = 4.85, 95% CI [1.52, 15.46]), bleeding between periods (rrr = 3.26, 95% CI [1.32, 8.04]) and pelvic or back pain (rrr = 2.79, 95% CI [1.18, 6.58]) were associated with suspicious for cancer.ConclusionAbout 8.9% and 3.96% of the women were positive for pre-cancerous cervical lesion and suspicious for cancer, respectively. The prevalence of pre-cancerous cervical lesion is high as compared to other regional prevalence in the country. Marital status, education, sexually transmitted infection, bleeding, and pelvic pain were risk factors of pre-cancerous cervical lesion'. This finding implies that the sexual exposure, having no permanent husband and being not educated attributes to the high prevalence of pre-cancerous cervical lesion and may aggravate the transmission of HPV."

Dataset Information

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

Publications

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

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