Thesis

185 Dynamics of methylated cell-free DNA in the urine of non-small cell lung cancer patients Table 3: Parameter estimates of DNA methylation levels of CDO1, SOX17 and TAC1 measured over time in urine samples of NSCLC patients according to the fitted linear mixed model. CDO1 SOX17 TAC1 Fixed effects Estimates 95%-CI p Estimates 95%-CI p Estimates 95%-CI p (Intercept) 0.80 (0.39, 1.20) 0.83 (0.48, 1.17) 0.14 (-0.11, 0.38) day [2] -0.14 (-0.32, 0.04) 0.136 -0.06 (-0.25, 0.13) 0.528 0.01 (-0.18, 0.20) 0.915 time [afternoon] -0.09 (-0.27, 0.09) 0.343 -0.10 (-0.29, 0.09) 0.295 0.10 (-0.09, 0.28) 0.313 time [evening] -0.07 (-0.22, 0.08) 0.379 -0.05 (-0.21, 0.10) 0.511 0.03 (-0.12, 0.18) 0.674 DNA concentration 0.08 (0.01, 0.15) 0.026 0.21 (0.14, 0.28) <0.001 0.08 (0.02, 0.14) 0.005 Random Effects σ2 0.19 0.20 0.20 τ00 subject 0.55 0.27 0.03 ICC 0.74 0.57 0.14 N subject 23 23 23 Observations* 133 133 133 DNA methylation level estimates are presented as square root transformed ct ratios. Methylation levels of all markers were independent of sex, age, weight, therapy during urine collection, survival, tumor stage, and tumor histology. σ2 = within-subject variability; τ00 = between-subject variability; ICC = Intraclass Correlation Coefficient; NSCLC = non-small cell lung cancer. *Five urine samples were excluded from the analysis based on an ACTB Ct value of ≥ 32. 7

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