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Page 54 Ding et al. J Transl Genet Genom 2021;5:50-61 I http://dx.doi.org/10.20517/jtgg.2020.01

Figure 2. Differential gene expression for CD24 and SFRP4 between sample groups classified by patient age, sample type, or metastasis
factors. CD24 and SFRP4 are 2 of the 36 genes in the iPAM classifier. A and B, Gene expression data from the 119 COH patients were
used to generate the box and dot plots; there were significant tumor-vs.-matched-benign median expression differences among young
patients (≤ 50 years) with Gleason score of 7 for CD24 (A) and SFRP4 (B) (black vs. blue for young patients, FDR < 0.05); for CD24 (panel
A), median expression level was significantly higher in tumors from young patients than in tumors from old patients with Gleason score
of 7 (black vs. green, FDR < 0.05). C and D, Gene expression data for 545 patients in the Mayo discovery data set were used to generate
plots; among young (≤ 55 years) patients, significantly increased median expression levels for CD24 (C) and SFRP4 (D) were observed in
patients with metastasis compared to patients without metastasis (black vs. blue, FDR < 0.05); however, no significant median expression
difference related to metastasis status among patients older than 70 years (red vs. green, P > 0.2).

developing metastasis. For the three independent data sets (MC II, CC, TJU, n = 556) with follow-up time
from the date of RP, 75 of 556 patients (13.5%) developed metastasis within five years after RP (early),
60 patients (10.8%) developed metastasis more than five years after RP (late), and 421 patients had no
metastases at last follow-up (mean follow-up time of 91 months). The median iPAM risk scores for the
three groups of patients were 0.89, 0.67, and 0.24, respectively. The iPAM risk scores were stratified into
high-, intermediate-, and low-risk groups by two cut points of 0.4 and 0.6 determined by the distribution of
risk score [Supplementary Figure 1]; the three groups showed highly significant differences in metastasis-
free survival (P < 0.0001) [Figure 3A]. Of 75 patients who developed metastasis within five years of RP,
69 patients (92%) were classified in either the high-risk group (58 patients) or intermediate-risk group
(11 patients). The AUC of five-year survival ROC for the iPAM classifier was 0.82 (95%CI: 0.77-0.86),
outperforming the AUC [0.69 (95%CI: 0.61-0.75)] for the clinical classifier assembled based on six clinical
variables [Supplementary methods]. With a combined clinical and iPAM classifier, the AUC was 0.80
(95%CI: 0.75-0.85).