SUPPLEMENTARY MATERIAL (Online Only) s1

SUPPLEMENTARY MATERIAL (online only)

SUPPLEMENTARY TABLES

Table S1 Summary of differentially expressed genes associated with prenylated PTP activity during cancer progression in the BC transcriptome (GSE32894) Comparing T2-4 to Ta-1 Probe Gene Symbol Biological Process Molecular Function Log ratio P value hydrolase activity, identical protein ILMN_1662427 0.1478 0.0019 PTP4A3 protein amino acid dephosphorylation binding, prenylated protein tyrosine phosphatase activity hydrolase activity, identical protein ILMN_1769779 0.2034 0.0002 PTP4A3 protein amino acid dephosphorylation binding, prenylated protein tyrosine phosphatase activity hydrolase activity, identical protein ILMN_2359710 0.1826 0.0005 PTP4A3 protein amino acid dephosphorylation binding, prenylated protein tyrosine phosphatase activity hydrolase activity, prenylated ILMN_2338997 -0.2915 <0.0001 PTP4A2 protein amino acid dephosphorylation protein tyrosine phosphatase activity, protein binding

1 Table S2 Association between PTP4A3 expression and clinicopathological factors of MIBC Parameter Category Case No. PTP4A3 Expression P value Low High Gender, no. (%) Male 91 (74) 29 (32) 62 (68) 0.795 Female 32 (26) 11 (34) 21 (66) Age (years), no. (%) < 65 51 (41) 13 (25) 38 (75) 0.161 ≥ 65 72 (59) 27 (37) 93 (63) Primary tumor (T), no. (%) T2 53 (43) 26 (49) 27 (51) 0.003* T3 49 (40) 10 (20) 39 (80) T4 21 (17) 4 (19) 17 (81) Nodal metastasis, no. (%) Negative (N0) 94 (76) 35 (37) 59 (63) 0.045* Positive (N1-2) 29 (24) 5 (17) 24 (83) Histological grade, no. (%) Low grade 2 (2) 1 (50) 1 (50) 0.546 High grade 121 (98) 39 (32) 82 (68) Vascular invasion, no. (%) Absent 75 (61) 27 (36) 48 (64) 0.303 Present 48 (39) 13 (27) 35 (73) Perineural invasion, no. (%) Absent 106 (86) 36 (34) 70 (66) 0.394 Present 17 (14) 5 (24) 13 (76) Mitotic rate (per 10 high < 10 45 (37) 16 (36) 29 (64) 0.585 power fields), no. (%) ≥ 10 78 (63) 24 (31) 54 (69)

2 * Statistically significant

3 Table S3 Association between PTP4A3 expression and clinicopathological factors of NMIBC Parameter Category Case No. PTP4A3 Expression P value Low High Gender, no. (%) Male 125 (73) 76 (61) 49 (39) 0.534 Female 47 (27) 31 (66) 16 (34) Age (years), no. (%) < 65 70 (41) 53 (76) 17 (24) 0.002* ≥ 65 102 (59) 54 (53) 48 (47) Primary tumor (T), no. (%) Ta 84 (49) 44 (52) 40 (48) 0.009* T1 88 (51) 63 (72) 25 (28) Nodal metastasis, no. (%) Negative (N0) 172 (100) 107 (62) 65 (38) - Positive (N1-2) 0 (0) 0 (0) 0 (0) Histological grade, no. (%) Low grade 54 (31) 33 (61) 21 (39) 0.841 High grade 1118 (69) 74 (63) 44 (37) Vascular invasion, no. (%) Absent 171 (99) 107 (63) 64 (37) 0.378 Present 1 (1) 0 (0) 1 (100) Perineural invasion, no. (%) Absent 169 (98) 106 (63) 63 (37) 0.558 Present 3 (2) 1 (33) 2 (67) Mitotic rate (per 10 high < 10 94 (55) 52 (55) 42 (45) 0.041* power fields), no. (%) ≥ 10 78 (45) 55 (71) 23 (29)

4 * Statistically significant

5 Table S4 Univariate and multivariate analyses predicting CSS and MFS in patients with MIBC Parameter Category Case No. CSS MFS Univariate analysis Univariate analysis Multivariate analysis No. of event H.R. 95% C.I. P value No. of event H.R. 95% C.I. P value Gender Male 91 35 - - - 41 - - - Female 32 7 - - - 8 - - - Age (years) < 65 51 14 - - - 19 - - - ≥ 65 72 28 - - - 30 - - - Primary tumor (T) T2 53 17 - - - 16 - - - T3-4 70 25 - - - 33 - - - Nodal metastasis Negative (N0) 94 31 - - - 34 - - - Positive (N1-2) 29 11 - - - 15 - - - Histological grade Low grade 2 0 - - - 0 - - - High grade 121 42 - - - 49 - - - Vascular invasion Absent 75 27 - - - 27 - - - Present 48 15 - - - 22 - - - Perineural invasion Absent 106 34 1 0.019* 39 1 0.033* Present 17 8 2.602 1.167-5.801 10 2.162 1.065-4.391 Mitotic rate (per 10 < 10 45 5 1 0.001* 11 1 0.013* high power fields) ≥ 10 78 37 4.626 1.814-11.798 38 2.354 1.200-4.616 PTP4A3 expression Low 40 8 1 0.005* 10 1 0.013* High 83 34 3.178 1.414-7.141 39 2.463 1.214-4.998 * Statistically significant

6 Table S5 Univariate and multivariate analyses predicting CSS, MFS, and RFS in patients with NMIBC Parameter C Case CSS RFS a No. Univariate analysis Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis t e Event P value H.R. 95% C.I. P Event P value H.R. 95% C.I. P value Event P value H.R. 95% C.I. P g value o r y Gender M 125 6 0.3126 - - - 19 0.7298 - - - 46 0.3389 - - - a l e F 47 4 - - - 8 - - - 19 - - - e m a l e Age (years) < 70 3 0.3463 - - - 12 0.9451 - - - 30 0.3871 - - -

6 5 ≥ 102 7 - - - 15 - - - 35 - - -

6 5 Primary T 84 1 0.0286* 1 0 4 0.0003* 1 <0.001* 27 0.0212* 1 0.350 tumor (T) a . T 88 9 11.445 1.444-90.681 23 7.000 2.418-20.265 38 1.331 0.730-2.427 1 Nodal N 172 10 - - - - 27 - - - - 65 - - - - metastasis e g a t i v e P 0 0 - - - 0 - - - 0 - - - o s i t i 7 v e Histological L 54 2 0.3453 - - - 5 0.0699 - - - 15 0.0121* 1 0.109 grade o w

g r a d e H 118 8 - - - 22 - - - 50 1.789 0.878-3.646 i g h

g r a d e Vascular A 171 10 0.9401 - - - 27 0.9165 - - - 65 0.7719 - - - invasion b s e n t P 1 0 - - - 0 - - - 0 - - - r e s e n t Perineural A 169 10 0.7685 - - - 27 0.6130 - - - 64 0.4824 - - - invasion b s e n t P 3 0 - - - 0 - - - 1 - - - r e s e n 8 t Mitotic rate < 94 7 0.5562 - - - 12 0.0587 - - - 35 0.1877 - - - (per 10 high power fields) 1 0 ≥ 78 3 - - - 15 - - - 30 - - -

1 0 PTP4A3 L 107 2 0.0384* 1 0 14 0.9303 - - - 40 0.3258 - - - expression o . w H 65 8 5.348 1.114-25.689 13 - - - 25 - - - i g h * Statistically significant