TY - JOUR
T1 - Methylation analysis in urine fractions for optimal CIN3 and cervical cancer detection
AU - van den Helder, Rianne
AU - van Trommel, Nienke E
AU - van Splunter, Annina P
AU - Lissenberg-Witte, Birgit I
AU - Bleeker, Maaike C G
AU - Steenbergen, Renske D M
N1 - Copyright © 2020. Published by Elsevier B.V.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - Cervical intraepithelial neoplasia
KW - Comparative analysis
KW - DNA Methylation
KW - Urine
UR - http://www.scopus.com/inward/record.url?scp=85081690695&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.pvr.2020.100193
DO - https://doi.org/10.1016/j.pvr.2020.100193
M3 - Article
C2 - 32171935
SN - 2405-8521
VL - 9
SP - 100193
JO - Papillomavirus research
JF - Papillomavirus research
M1 - 100193
ER -