Objective: To recognize a novel and optimized combination of epigenetic biomarkers capable of returning higher sensitivity and specificity synergistically in pathologically varied sample groups for urine sediment examination of bladder cancer (BlCa).
Methods: Methylation levels of seven candidate biomarkers (EOMES, GDF15, NID2, PCDH17, POU4F2, TCF21, and ZNF154) in 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients, and 30 healthy volunteers (HV) were quantified by qMSP using the sediment DNA of urine samples. Standard curves and receiver operating characteristic (ROC) curves were generated for each biomarker. The combining predictors of all the possible biomarker combinations were calculated through logistic regression model. Subsequently, the ROC curves of the three combinations that have yielded the best performing combining predictors were constructed.
Results: From the samples provided, the top three biomarker combinations (C) returned high sensitivity and specificity of 91.38% and 94.29% from PCDH17 + POU4F2 (C1), 91.38% and 90.00% from PCDH17 + POU4F2 + NID2 (C2), and 93.10% and 92.86% from PCDH17 + POU4F2 + EOMES (C3) consequently. These combinations provide greater sensitivities and specificities than any examined single biomarkers, except for C2, which has a lower specificity compare to POU4F2 (92.86%).
Conclusions: Compound biomarker panels were shown to be capable of detecting BlCa effectively by utilizing urine sediment DNA. Due to the performance of higher sensitivity and specificity when compared to single biomarker examinations in BlCa patients and the diverse control groups, these panels are particularly suitable for mass-scale routine BlCa screening.
