Article Abstract

Evaluation of DNA methylation in promoter regions of SFRP4 and ZAR1 in urine and plasma of women with cervical lesions

Authors: Rene Hoffstetter, Ismael Riquelme, Alejandra Andana, Carmen G. Ili, Kurt Buchegger, Hernán Vargas, Priscilla Brebi, Juan Carlos Roa


Background: Aberrant DNA hypermethylation in tumor suppressor genes is a common feature in cervical cancer (CC). This abnormal hypermethylation could be used as potential biomarkers for detecting CC in non-invasive samples such as urine and plasma.
Methods: This study aimed to evaluate in urine and plasma the methylation status of two genes previously found hypermethylated in CC (ZAR1 and SFRP4) and assesses their diagnostic value. Thus, DNA methylation was measured in 171 paired samples of urine and plasma taken from women with non-lesions [60], low-grade squamous intraepithelial lesions (L-SIL) [40], high-grade squamous intraepithelial lesions (H-SIL) [40] and cervical squamous cell carcinoma (SCC) [31] by quantitative methylation-specific PCR (QMSP).
Results: In urine, a significant difference was observed for methylation levels of SFRP4 between cancer group and all the other groups (P<0.005), but not for ZAR1. The ROC analysis in urine showed an AUC of 0.633 for both genes, with a specificity of 83.3% and a sensitivity of 45.16%. In plasma, there were no significant differences of DNA methylation levels either for ZAR1 or SFRP4 genes between the studied groups; however, an AUC of 0.6333 was obtained with a sensitivity of 93.55%.
Conclusions: Hypermethylation of SFRP4 promoter region in urine could be used as CC biomarker within a panel of methylated genes.