Methylation analysis in urine fractions for optimal CIN3 and cervical cancer detection

IF 3.2 Papillomavirus Research Pub Date : 2020-06-01 DOI:10.1016/j.pvr.2020.100193

Rianne van den Helder , Nienke E. van Trommel , Annina P. van Splunter , Birgit I. Lissenberg-Witte , Maaike C.G. Bleeker , Renske D.M. Steenbergen

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引用次数: 14

Abstract

Introduction

Urine sampling is an interesting solution for CIN3 and cervical cancer detection. Urine can be separated in different fractions: full void urine, urine sediment and urine supernatant. We aimed to determine which urine fraction is most competent for CIN3 and cervical cancer detection by methylation analysis.

Methods

Urine samples (27 controls, 30 CIN3 and 17 cervical cancer) were processed into 3 fractions and tested for 5 methylation markers (ASCL1, GHSR, LHX8, SST, ZIC1). We determined Spearman correlation coefficients between fractions, compared methylation levels and calculated AUCs for CIN3 and cancer detection.

Results

In general strong correlations (r > 0.60) were found between urine fractions. Methylation levels increased significantly with severity of underlying disease in all urine fractions. CIN3 and controls differed significantly for 2 markers in full void urine, 4 markers in urine sediment and 1 marker in urine supernatant, with AUCs of 0.55–0.79. Comparison of cancer to controls was highly significant for all markers in all fractions, yielding AUCs of 0.87–0.99.

Conclusion

Methylation analysis performs excellent in all urine fractions for cervical cancer detection. Our results indicate the potential of CIN3 detection by urinary methylation analysis, and demonstrate that urine sediment performs best to detect CIN3.

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尿组分甲基化分析对CIN3和宫颈癌的最佳检测

尿液取样是CIN3和宫颈癌检测的一种有趣的解决方案。尿液可分为不同的馏分:全空尿、尿沉渣和尿上清。我们的目的是通过甲基化分析确定哪个尿液部分最能用于CIN3和宫颈癌检测。方法将27例对照组、30例CIN3、17例宫颈癌患者的尿样分成3组，检测5种甲基化标志物(ASCL1、GHSR、LHX8、SST、ZIC1)。我们确定了分数之间的Spearman相关系数，比较了甲基化水平，并计算了CIN3和癌症检测的auc。结果一般强相关性(r >0.60)。所有尿液中甲基化水平随潜在疾病的严重程度显著增加。全空尿中2个标志物、尿沉渣中4个标志物和尿上清中1个标志物与对照组差异显著，auc为0.55 ~ 0.79。癌症与对照组的比较在所有部分的所有标记上都是高度显著的，得到0.87-0.99的auc。结论甲基化分析在宫颈癌检测中具有良好的效果。我们的研究结果表明了通过尿甲基化分析检测CIN3的潜力，并表明尿沉积物是检测CIN3的最佳方法。

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来源期刊

Papillomavirus Research VIROLOGY-

自引率

0.00%

发文量

审稿时长

14 weeks

期刊介绍： The official Journal of the International Papillomavirus Society Papillomavirus Research (PVR), the Journal of HPV and other Small DNA Tumor Viruses publishes innovative papers related to all aspects of papillomaviruses and other small DNA tumor viruses. The official journal of the International Papillomavirus Society, PVR is an open access publication that aims to bring together virologists, immunologists, epidemiologists and clinicians working in the booming field of HPV and animal papillomaviruses, polyomaviruses and other small DNA tumor viruses and their associated diseases, in order to foster and facilitate interdisciplinary communication. The journal welcomes original research articles, reviews, short communications, opinion articles and regional update reports on papillomaviruses and other tumor viruses in the following sections: a. Biology of papillomaviruses and related viruses from life cycle to cancer b. Epidemiology etiology and natural history studies c. Natural and induced immunity including vaccine research d. Intervention studies and strategies including i. Clinical studies and trials ii. HPV treatments iii. HPV vaccination programs iv. Diagnostics and screening e. Infection and disease prevention, modeling studies f. Guidelines and public health recommendations g. HPV Studies in special populations Regional and local studies on these viruses.