59 DNA methylation markers for endometrial cancer Methylation marker performance for EC detection Table 2 provides an overview of individual DNA methylation markers for EC detection in minimally invasive specimens. Markers with a high diagnostic accuracy (i.e. AUC ≥ 0.80) are marked in bold. Among the 32 genes investigated in the final article selection, 15 individual genes most competent for EC detection were selected, including ADCYAP1 (25, 27), ASCL2 (27), BHLHE22 (13, 24), CDH13 (25, 27), CDO1 (13, 24), CELF4 (24), GALR1(28), HAND2 (29), HS3ST2 (27), HTR1B (25), MAGI2 (16), MME (25, 27), POU4F3 (16), RASSF1 (25), and ZNF662 (24), with AUC values ranging from 0.80 to 0.96. Table 2: Performance of individual DNA methylation markers in minimally invasive specimens for distinguishing endometrial carcinoma from benign endometrium. Gene AUC (95% CI) Sensitivity % Specificity % Cytological sample type Study (year) Ref. ADCYAP1 0.88 (U) U U Endometrial brushes BakkumGamez (2015) (25) ADCYAP1 0.67 (U) U U Vaginal tampons BakkumGamez (2015) (25) ADCYAP1 0.86 (0.76 – 0.96) U U Endometrial brushes Wentzensen (2014) (27) ASCL2 0.76 (U) U U Endometrial brushes BakkumGamez (2015) (25) ASCL2 0.69 (U) U U Vaginal tampons BakkumGamez (2015) (25) ASCL2 0.81 (0.70 – 0.92) U U Endometrial brushes Wentzensen (2014) (27) BHLHE22 0.95 (0.91 – 0.99) 83.7 93.7 Cervical scrapes Huang (2017) (24) BHLHE22 0.88 (U) U U Cervical scrapes Liew (2019) (13) CADM1 U (U) U U Cervical scrapes De Strooper (2014) (30) CDH13 0.86 (U) U U Endometrial brushes BakkumGamez (2015) (25) CDH13 0.67 (U) U U Vaginal tampons BakkumGamez (2015) (25) CDH13 0.86 (0.76 – 0.96) U U Endometrial brushes Wentzensen (2014) (27) CDO1 0.95 (0.91 – 0.98) 82.0 93.8 Cervical scrapes Huang (2017) (24) CDO1 0.84 (U) U U Cervical scrapes Liew (2019) (13) CELF4 0.94 (0.90 – 0.97) 96.0 78.7 Cervical scrapes Huang (2017) (24) GALR1 0.93 (0.87 – 0.97) 92.7 78.9 Vaginal swabs Doufekas (2013) (28) GTF2A1 0.55 (U) U U Vaginal tampons BakkumGamez (2015) (25) 3
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