Assessing methylation status of PAX1 in cervical scrapings as a novel diagnostic and predictive biomarker was closely related to screen cervical cancer

摘要

Objective: Previous studies have demonstrated that levels of hypermethylation of paired boxed gene 1 in cervical tissues are associated with the grades of severities of cervical neoplasia in women, which suggests that testing for DNA methylation has a potential role in neoplasma screening. In this study, by testing methylation levels of PAX1 genes in cervical scrapings and cervical tissues of different lesion levels, aims to evaluate the diagnostic value of DNA methylation testing as a biomarker for early detecting cancerous changes in cervical tissues and to compare the efficacy between PAX1 methylation test and HPV test in detecting of cervical cancer. Methods: A total of 121 cervical scrapings were analyzed, including normal (n = 28), cervical intraepithelial neoplasm 1 (CIN1; n = 32), CIN2/3 (n = 34), and invasive cancer (n = 27), which were all diagnosed by pathologic examination. Results: The values of PAX1 methylation reference in invasive cancer (mean [SE], 26.3 [3.5]) was significantly higher than CIN2/3 (13. 2 [2.2]) and the CIN1 (4.5 [0.45]; P < 0.001). The PAX1 promoter was hypermethylated in 100% of invasive cancer tissue compared with 0% of normal tissue, 9% of CIN1, 44% of CIN2/3 (P < 0.01). Methylation levels of cervical scrapings and cervical tissues represent strong consistency within each group. In contrast, the HPV test result was positive in 17% of normal tissue, 81% of CIN1, 91% of CIN2/CIN3, and 92% of invasive cancer. Based on receiver operating characteristic (ROC) analysis, hypermethylation of PAX1 was a significant candidate in segregating cervical cancer from normal/cervical neoplasia cases (P < 0.001). At an optimal cutoff value, sensitivity and specificity between 80% and 93% were obtained. In conclusion, the current results indicated that the methylation density of PAX1 by pyrosequencing in cervical scrapings held a great promise for cervical cancer screening.