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Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population.

ABSTRACT: A case-control study was used to explore the association between the methylation status in the promoter regions of the cGAS, MAVS, and TRAF3 genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The cGAS, MAVS, and TRAF3 promoter methylation levels in CPL (CPL cGAS = 35.40%, CPL MAVS = 24.26%, and CPL TRAF3 = 96.76%) were significantly higher than those in the control (Control cGAS = 31.87%, Control MAVS = 21.16%, and Control TRAF3 = 96.26%, PcGAS < 0.001, PMAVS < 0.001, and PTRAF3 = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose cGAS methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (ORa = 2.49, 95% CI = 1.31-4.75, P a = 0.006). The women with MAVS methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (ORa = 1.97, 95% CI = 1.06-3.69, P a = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of cGAS and MAVS in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in cGAS, MAVS, and TRAF3 genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in cGAS and MAVS genes and hrHPV infection might play a role in the development of CPL.

SUBMITTER: Huang S

PROVIDER: S-EPMC6868924 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS:Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS:Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS:We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.

Project description:Background Cervical cancer is the most prevalent gynecologic cancer in women and the second leading cause of cancer death worldwide. Africa's southern, eastern, and western regions have the highest rates of cervical cancer. Cervical cancer is treatable and curable when detected early, but it is nonetheless fatal in low- and middle-income (LMIC) nations where screening and early detection are not widely accessible. Objective The objective of this study is to assess the magnitude of precancerous cervical lesions and their associated factor among women screened for cervical cancer at a referral center in southern Ethiopia, in 2021. Methods A retrospective institution-based cross-sectional study was conducted from February 21 to April 14, 2022, among randomly selected 372 records of women screened for cervical cancer at Hawassa University Specialized Hospital. Data were extracted from clients' charts using a data extraction checklist. Statistical Package for Social Sciences version 26 and logistic regression analysis were applied to determine the association between dependent and independent variables, and significance was declared at p-value <0.05. Results The magnitude of abnormal cervical dysplasia in this study was 18.3% of which 14% were precancerous cervical lesions and 4.3% were cervical cancer. Early coitarche: Adjusted odds ratio (AOR) = 5.6 [95% (confidence interval) CI = 1.87–16.78], having more than one sexual partner: AOR = 2.6 [95% CI = 1.2–5.68], being HIV positive: AOR = 3.56 [95% CI = 1.53–8.29], and having sexually transmitted infections: AOR = 4.64 [95% CI = 2.08–10.35] were independent predictors of precancerous cervical lesions. Conclusion The magnitude of precancerous cervical lesions in the study setting is 18% and the magnitude of cervical cancer is 14%, which is higher than the pooled prevalence of precancerous cervical lesions in Ethiopia. Having multiple sexual partners, being HIV positive, having sexual intercourse before 21 years, and new STI diagnosis was independently associated with abnormal precancerous cervical lesions.

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Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population.

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