Optimization of methylated DNA markers to rule out endometrial cancer in patients with abnormal uterine bleeding.
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Bakkum-Gamez Jamie N, Harrington Shariska P, Slettedahl Seth W, Berger Calise K, Krakowski Katelyn N, Lemens Maureen A, Burger Kelli N, Gonser Anna M, Taylor William R, Mahoney Douglas W, Foote Patrick H, Sherman Mark E, Laughlin-Tommaso Shannon K, Hopkins Matthew R, Butler Kristina A, DeStephano Christopher C, Schoolmeester J Kenneth, Phifer-Combs Olivia, McCullagh Kelly, AlHilli Mariam M, Davidson Emily R W, Uribasterra Pablo, Saad Andre Hani, Miller Joyce, Kilts Toni M, Finkelstein Kenneth, Lievano Guillermo, Mills Kathryn A, Lessard-Anderson Collette R, Gattoc Leda Portia, Kroll Laura, Narula Gagandeep, Schroeder Paige, Hanson Hallie, Harings Kathleen, Krockenberger Martin, Beer Tomasz M, Kielar-Grevstad Elle, Gagrat Bridget Z, Olson Marilyn C, Kisiel John B
Аннотация
METHODS: Patients with AUB/PMB ≥45 years or EC or atypical endometrial hyperplasia (AEH) ≥18 years were prospectively enrolled to self-collect vaginal fluid using a tampon. Bisulfite-converted DNA from vaginal fluid was assayed with long-probe quantitative amplified signal (LQAS) for the quantification of MDM signal. Samples were tested with the goal of building a parsimonious model to discriminate EC from benign endometrium (BE). This marker reduction study started with 19 previously identified MDMs. Down-selection was then performed on a panel of 12 MDMs in an independent marker selection study. A random forest model was developed and validated in an independent test set.
RESULTS: In marker reduction, a 19-MDM model achieved a sensitivity of 91% (83-96%) in EC with a specificity of 87% (80-92%) observed in BE in an independent set. In marker selection, a 2-MDM model generated a sensitivity for EC of 96% (84-99%), specificity of 82% (67-91%), and an AUC of 0.97 (0.94-1) in an independent test set.
CONCLUSIONS: Rigorous marker reduction from 19 MDMs to 12 allowed for marker selection of a 2-MDM panel with high sensitivity and specificity to detect EC in vaginal fluid.