Dataset Information

A Sensitive and Simplified Classifier of Cervical Lesions Based on a Methylation-Specific PCR Assay: A Chinese Cohort Study.

ABSTRACT: Objective:The aim of this study is to assess the diagnostic and screening performance of a standardized methylation-specific real-time PCR assay targeting SOX1 and PAX1 genes for cervical cancer in a Chinese cohort. Methods:Genomic DNA was extracted from cervical exfoliated cells and converted by sodium bisulfite and then analyzed by qMSP assay. Ct values were collected for PAX1 and SOX1 as target genes and ?-actin as an endogenous reference gene. The samples included 295 cervicitis, 111 LSIL (low-grade squamous intraepithelial lesion), 51 HSIL (high-grade squamous intraepithelial lesion) and 30 cervical cancer. Results:The Ct values decreased with the progression of cervical cancer from cervicitis, through LSIL and HSIL to cancer. The difference in Ct values between cytological grades was highly significant (p?0.01) between grades either for PAX1 or for SOX1 except the difference between cervicitis and LSIL of SOX1. With the Ct cut-off values of PAX1 gene and SOX1 gene 38.6 and 38 and with the PAX1/SOX1 in combination, the positive rate of methylation in invasive cancer tissues was 100%, in contrast to 11.5% (95% CI: 8.67%-14.33%) in cervicitis tissues, 45.1% (95% CI: 40.68%-49.52%) in LSIL tissues, and 68.5% (95% CI: 64.37%-72.63%) in HSIL tissues. The specificity and sensitivity of differentiating tumors from cervicitis were 0.957 (95% CI: 0.939-0.975) and 1.00, respectively. The specificity and sensitivity of differentiation between cervicitis+LSIL and HSIL+cervical cancer were 0.881 (95% CI: 0.852-0.91) and 0.748 (95% CI: 0.709-0.787), respectively. Conclusion:PAX1/SOX1 methylation could be translated into clinical practice for cervical neoplasia detection.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7167279 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Sensitive and Simplified Classifier of Cervical Lesions Based on a Methylation-Specific PCR Assay: A Chinese Cohort Study.

Zhang Lei L Yu Jing J Huang Wenxian W Zhang Hongping H Xu Jian J Cai Hongning H

Cancer management and research 20200415

<h4>Objective</h4>The aim of this study is to assess the diagnostic and screening performance of a standardized methylation-specific real-time PCR assay targeting <i>SOX1</i> and <i>PAX1</i> genes for cervical cancer in a Chinese cohort.<h4>Methods</h4>Genomic DNA was extracted from cervical exfoliated cells and converted by sodium bisulfite and then analyzed by qMSP assay. Ct values were collected for <i>PAX1</i> and <i>SOX1</i> as target genes and <i>β-actin</i> as an endogenous reference gene ...[more]

PMID: 32346310

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Project description: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.

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Dataset Information

A Sensitive and Simplified Classifier of Cervical Lesions Based on a Methylation-Specific PCR Assay: A Chinese Cohort Study.

Publications

A Sensitive and Simplified Classifier of Cervical Lesions Based on a Methylation-Specific PCR Assay: A Chinese Cohort Study.

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