Fig. 3
Frequency and prognostic value of mPITX3 and mPITX2 in the training (n = 498) and validation (n = 300) cohorts. PITX3 and PITX2 DNA methylation was analyzed in prostate carcinoma patients from two cohorts. Methylation frequencies (a, c, and e) and Kaplan-Meier analyses of BCR-free survival in patients stratified according to dichotomized mPITX3 and mPITX2 levels are shown (b, d, and f). a mPITX3 analysis in the training cohort revealed a symmetric, bell-shaped distribution covering a broad spectrum of values (22–92 %). An optimal cutoff was elaborated by an iterative approach (68.2 %) stratifying patients into mPITX3 hyper- (mPITX3 high) and hypomethylated (mPITX3 low) cases. b Patient survival in the training cohort according to mPITX3 low and mPITX3 high status. Patients with mPITX3 low tumors show a better prognosis. Approximate mean BCR-free survival: 93 months (mPITX3 low, 95 % CI 85–100 months, n = 301) and 76 months (mPITX3 high, 95 % CI 63–90 months, n = 117; LR = 5.05; p = 0.025), respectively. c mPITX2 analysis in the training cohort revealed an uneven distribution covering an altogether lower spectrum of values than mPITX3 (5–79 %). An optimal cutoff was elaborated by an iterative approach (34.3 %) stratifying patients into mPITX2 hyper- (mPITX2 high) and hypomethylated (mPITX2 low) cases. d Patient survival in the validation cohort according to mPITX2 low and mPITX2 high status. Patients with mPITX2 low tumors show a better prognosis. Approximate mean BCR-free survival: 96 months (mPITX2 low, 95 % CI 88–105 months, n = 220) and 78 months (mPITX2 high, 95 % CI 67–89 months, n = 198; LR = 7.95; p = 0.005), respectively. e mPITX3 analysis in the validation cohort revealed a flattened, bell-shaped distribution covering (5–100 %). An optimal cutoff was elaborated by an iterative approach (61.8 %) stratifying patients into mPITX3 hyper- (mPITX3 high) and hypomethylated (mPITX3 low) cases. f Patient survival in the validation cohort according to mPITX3 low and mPITX3 high status. Patients with mPITX2 low tumors show a better prognosis. Approximate mean BCR-free survival: 125 months (mPITX3 low, 95 % CI 118–132 months, n = 145) and 103 months (mPITX3 high, 95 % CI 91–115 months, n = 105; LR = 11.17; p = 0.001), respectively. Patient survival in the validation cohort according to mPITX2 low and mPITX2 high status is reported elsewhere [30]