{
    "abstract": "DNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer.\nThe histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect\u00ae) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect\u00ae assay for CIN2 or worse (CIN2\u2009+) and CIN3 or worse (CIN3\u2009+) were evaluated.\nAccording to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P\u2009=\u20090.000). The methylation score above 1.1 was more common in CIN2\u2009+\u2009than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P\u2009=\u20090.033, 0.000 and 0.000, respectively), except for CIN2 (P\u2009=\u20090.171). While the positive rate of GynTect\u00ae in each paired group had no difference (all P\u2009>\u20090.05). The positive rate of every methylation marker in the GynTect\u00ae assay showed differences in four cervical lesion groups (all P\u2009<\u20090.05). The specificity of GynTect\u00ae assay for detection of CIN2\u2009+\u2009/CIN3\u2009+\u2009were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect\u00ae/ZNF671 were significantly higher in CIN2\u2009+\u2009: odds ratio (OR) 5.271/OR 13.909, and in CIN3\u2009+\u2009: OR 11.022/OR 39.150, (all P\u2009<\u20090.001).\nThe promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect\u00ae assay based on cervical specimens provides diagnostic values for detecting CIN2\u2009+\u2009and CIN3\u2009+\u2009.",
    "authors": [
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Liye",
            "initials": "L",
            "lastname": "Shi"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Xue",
            "initials": "X",
            "lastname": "Yang"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Ling",
            "initials": "L",
            "lastname": "He"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Chunying",
            "initials": "C",
            "lastname": "Zheng"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Zhen",
            "initials": "Z",
            "lastname": "Ren"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Juweria Abdisamad",
            "initials": "JA",
            "lastname": "Warsame"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Suye",
            "initials": "S",
            "lastname": "Suye"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Lei",
            "initials": "L",
            "lastname": "Yan"
        },
        {
            "affiliation": "Department of Clinical Medicine, Harbin Medical University, Harbin, 150081, China.",
            "firstname": "Haiyi",
            "initials": "H",
            "lastname": "Cai"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.",
            "firstname": "Xiao",
            "initials": "X",
            "lastname": "Xiao"
        },
        {
            "affiliation": "Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China. fuchun0814@csu.edu.cn.",
            "firstname": "Chun",
            "initials": "C",
            "lastname": "Fu"
        }
    ],
    "conclusions": "The promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect\u00ae assay based on cervical specimens provides diagnostic values for detecting CIN2\u2009+\u2009and CIN3\u2009+\u2009.",
    "copyrights": "\u00a9 2023. The Author(s).",
    "doi": "10.1186/s12885-023-10628-5\n10.3322/caac.21492\n10.3390/ijms20092262\n10.1038/nrc3728\n10.1002/ijc.33566\n10.1038/s41379-020-0528-x\n10.1007/s13277-014-1737-z\n10.1016/j.ebiom.2019.10.053\n10.1111/1471-0528.16395\n10.1080/15592294.2018.1507197\n10.3390/ijms22126463\n10.3389/fgene.2019.01123\n10.1007/s12094-020-02416-5\n10.1007/s13277-015-4197-1\n10.1158/1055-9965.EPI-20-0833\n10.1136/bmjopen-2019-029017\n10.1371/journal.pone.0091905\n10.1186/s12885-018-5125-8\n10.1186/s13148-017-0419-2\n10.1097/PGP.0b013e31826916c7\n10.1007/s00292-016-0230-4\n10.2147/CMAR.S225067\n10.1177/0963689718817478\n10.1097/LGT.0000000000000181\n10.1002/cncy.21521\n10.1158/1055-9965.EPI-20-1003\n10.1016/j.ygyno.2020.12.038\n10.1016/j.jviromet.2021.114219\n10.3389/fonc.2018.00099\n10.1097/LGT.0000000000000494\n10.3389/fonc.2019.00342\n10.1007/s00281-019-00773-0\n10.2217/epi-2019-0331\n10.1038/s41416-019-0593-4",
    "journal": "BMC cancer",
    "keywords": [
        "Cervical cancer",
        "Cervical intraepithelial neoplasia",
        "DNA methylation",
        "GynTect\u00ae assay",
        "High-risk human papillomavirus"
    ],
    "methods": null,
    "publication_date": "2023-02-22",
    "pubmed_id": "36803573\n30207593\n31067838\n24854082\n33729551\n32249820\n24554414\n31732479\n32619334\n30079796\n34208758\n31803230\n32514824\n26459314\n33441308\n31289088\n24647315\n30509219\n29090037\n23202792\n27738815\n32636674\n30545241\n26855142\n25931431\n33187968\n33451725\n34175345\n29707519\n31714325\n31134149\n31919577\n32938193\n31616037",
    "results": "According to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P\u2009=\u20090.000). The methylation score above 1.1 was more common in CIN2\u2009+\u2009than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P\u2009=\u20090.033, 0.000 and 0.000, respectively), except for CIN2 (P\u2009=\u20090.171). While the positive rate of GynTect\u00ae in each paired group had no difference (all P\u2009>\u20090.05). The positive rate of every methylation marker in the GynTect\u00ae assay showed differences in four cervical lesion groups (all P\u2009<\u20090.05). The specificity of GynTect\u00ae assay for detection of CIN2\u2009+\u2009/CIN3\u2009+\u2009were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect\u00ae/ZNF671 were significantly higher in CIN2\u2009+\u2009: odds ratio (OR) 5.271/OR 13.909, and in CIN3\u2009+\u2009: OR 11.022/OR 39.150, (all P\u2009<\u20090.001).",
    "title": "Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens.",
    "xml": "<Element 'PubmedArticle' at 0x788502676840>"
}