Detection Of HTERC，c-MYC And CDH13 Genes For Cervical Cancer Screening

ObjectiveIn order to improve the accuracy of cervical lesions screening, to provide more screening methods, and to find some biomarkers of cervical cancer risk, the present study was designed to detect amplification of h TERC and c-MYC, and detect promoter methylation of CDH13 gene for cervical cancer screening.MethodsFluorescence in situ hybridization(FISH) technique detects amplification of h TERC and c-MYC in cervical epithelial exfoliated cells from normal uterine cervix, benign lesions of uterine cervix, CIN1, CIN2, CIN3 and ICC. Methylation-sensitive high-resolution melting curve(MS-HRM) technique detects promoter methylation of CDH13 gene in formalin-fixed paraffin-embedded biopsies from benign lesions of uterine cervix, CIN1, CIN2, CIN3 and ICC.The experimental data is analyzed by using the rank sum test and ROC curve analysis.Results1、The area under the ROC curve(AUC) values of h TERC are all greaterthan 0.8 for detection certain cervical lesions and worse. The results showed that detection of h TERC may be useful for cervical cancer screening. For example, when amplification rate of h TERC is >4, the sensitivity is 57.01% and the specificity is 90.62% for discriminating over cervical intraepithelial neoplasia type1 and worse; when amplification rate of h TERC is >14, the sensitivity and specificity for discriminating over cervical intraepithelial neoplasia type2 and worse were 71.15% and 84.87%.2、Comparison with h TERC, the AUC value of c-MYC is greater than 0.8 only for detection over CIN3 and worse, but the AUC values are greater than 0.7 for detection other cervical lesions and worse. when amplification rate of c-MYC is >6, the sensitivity is 69.23% and the specificity is 84.03% for discriminating over CIN2 and worse; when amplification rate of c-MYC is >10, the sensitivity and specificity for discriminating over CIN3 and worse were 87.50% and 76.77%.3、Detection of cytology is better than h TERC or c-MYC for discriminating over cervical benign lesions and worse. There was no significant difference between detection of h TERC gene and cytology for discriminating over CIN1 and worse, but detection of cytology is better than c-MYC. There was no significant difference among them for discriminating over CIN2 and worse, respectively for discriminating over CIN3 and worse.4、For detection CIN2 and worse, combined testing of h TERC and c-MYChave greater sensitivity and specificity; combined testing of h TERC and c-MYC and Cytology have greater specificity and a little rolling sensitivity.All kinds of combined detection did not significantly improve sensitivity and specificity for detection CIN3 and worse.5、Promoter methylation of CDH13 gene could be detected in benign lesions. The AUC values of promoter methylation of CDH13 gene are about 0.58 for discriminating different cervical lesions, so ability of its screening is not enough good.ConclusionThe h TERC and c-MYC may be useful biomarkers for detection of cervical lesions and cancer. Detection promoter methylation of CDH13 gene could not be confirmed as a biomarker for the early diagnosis of uterine cervix lesions at present.