PAX1 Methylation as a Potential Biomarker for Cervical Cancer Screening
PAX1 Methylation as a Potential Biomarker for Cervical Cancer Screening
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DOI：
10.1097/igc.0000000000000155
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发表时间：
2014-06-01
影响因子：
4.8
通讯作者：
Liao, Cheng-I
中科院分区：
文献类型：
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作者：
Kan, Yuen-Yee;Liou, Yu-Ligh;Liao, Cheng-I
目的：DNA 甲基化是早期癌症检测的潜在生物标志物。先前的研究表明，几个基因的甲基化是检测 III 级或更严重的宫颈上皮内瘤变 (CIN3+) 的有希望的标记。本研究的目的是探讨DNA甲基化检测在宫颈癌筛查中的可行性。方法：从袁氏总医院招募了443名女性。使用宫颈刷收集宫颈刮片进行巴氏（Pap）试验，并使用细胞学数据进行分析。将刷上残留的细胞保存在4℃的磷酸盐缓冲盐溶液中直至DNA提取。然后，提取的 DNA 用于分子测试，包括人乳头瘤病毒分型以及 PAX1、SOX1 和 NKX6-1 基因甲基化水平的定量。巴氏试验结果异常的受试者接受阴道镜检查或活检，并在活检结果显示 CIN2+ 时进行锥切术或大手术。本组最终诊断均通过阴道镜或病理检查确诊。该研究经袁总医院机构审查委员会批准，所有分子检测均由ISO17025认证实验室进行。结果：PAX1(m)和SOX1(m)对于CIN3+病变检测的敏感性大于80%，PAX1(m)和NXK6-1(m)的特异性大于80%。 PAX1(m)单独检测的敏感性和特异性分别为86%和85%，而与巴氏试验联合检测时，敏感性和特异性分别为89%和83%。结论：PAX1(m)作为宫颈癌筛查的生物标志物显示出巨大的潜力。当将PAX1m检测纳入当前的筛查方案时，可以大大提高筛查的效率。此外，不必要的阴道镜检查和活检转诊次数最多可减少 60%。然而，为了进一步实施该筛查计划，有必要进行基于人群的前瞻性研究。
Objectives: DNA methylation is a potential biomarker for early cancer detection. Previous studies suggested that the methylations of several genes are promising markers for the detection of cervical intraepithelial neoplasia at grade III or worse (CIN3+). The purpose of the present study was to explore the feasibility of these DNA methylation testing in cervical cancer screening.Methods: A total of 443 women were recruited from the Yuan's General Hospital. Cervical scrapings were collected for Papanicolaou (Pap) test by using cervical brushes, and the cytological data were used for analysis. The residual cells on the brush were preserved in phosphate-buffered saline solution at 4 degrees C until DNA extraction. Then, the extracted DNA were used for molecular tests, which included human papillomavirus typing and quantification of the methylation levels for PAX1, SOX1, and NKX6-1 genes. Subjects who had abnormal Pap test results underwent colposcopy or biopsy with subsequent conization or major surgery when biopsy results revealed CIN2+. The final diagnosis for this group was confirmed by colposcopy or pathological examination. The study was approved by the institutional review board of Yuan's General Hospital, and all the molecular tests were performed by ISO17025 certified laboratories.Results: The sensitivity of PAX1(m) and SOX1(m) was greater than 80%, and the specificity of PAX1(m) and NXK6-1(m) was greater than 80% for the detection of CIN3+ lesions. PAX1(m) detection alone had a sensitivity and specificity of 86% and 85%, respectively, whereas when used as a cotest with the Pap test, the sensitivity and specificity were 89% and 83%, respectively.Conclusions: PAX1(m) showed great potential as a biomarker for cervical cancer screening. When incorporating PAX1m detection into current screening protocol, the efficacy of screening could be greatly improved. Moreover, unnecessary referral for colposcopy and biopsy could be reduced up to 60%. However, prospective population-based studies are necessary for further implementation of this screening program.