Supplementary Figure 1. Genetic network analysis of the differentially expressed between high- and low-risk groups

(A, B) Genetic network of differential expressed genes between high- and low-risk groups (P <

0.001, two-sample t-test) and their regulator genes was constructed by PathwayAssist (see Fig. 5).

From this network, EGF and PTGS2 as well as PPARA and SP1 were identified as common regulators of the overexpressed genes. (C) Genetic network constructed by differentially expressed genes and their target genes revealed FOS/JUN as common target genes. Whereas, combining of genetic networks of regulators and target genes showed TP53 (D) and TGFB1 (E) as commonly regulated and targeted genes in the overexpressed genes in the high-risk group compared to the low-risk group.

A. B. C. D.

E.

Supplementary Table 1. Summary of the class prediction results for 65 HCCs

CCP LDA 1NN 3NN NC SVM High- Low- High- Low- High- Low- High- Low- High- Low- High- Low- Predicted Subclass risk risk risk risk risk risk risk risk risk risk risk risk High-risk (N=31) 23 8 23 8 27 4 26 5 20 11 29 2 Low-risk (N=34) 0 34 2 32 0 34 1 33 0 34 0 34 Mean percent of correctly 88 85 94 91 83 97 classification (%) Significance of leave- p<0.01 p<0.01 p<0.01 P<0.01 P<0.01 p<0.01 one-out cross validation

The genes significantly different between the high- and low risk groups with optimized

significance level were used for class prediction. Leave-one-out cross-validation method was

used to compute misclassification rate based on 100 random permutations. Abbreviations: CCP;

Compound Covariate Predictor, LDA: Linear Discriminant Analysis, NC; Nearest Centroid, NN;

Nearest Neighbor, SVM; Support Vector Machine.

Supplementary Table 2. Functional enrichment analysis of the differentially up- and down-

regulated genes in high-risk group compared to low-risk group of early recurrence

Up-regulated genes GOID P-value GO name T-test Mean Log-rank test T- P-value, High- Low- Fold Probe ID Symbol P-value FDR HR P-value ID statistic permuted risk risk difference GO:0007015 (p=0.000098) actin filament organization 209435_s_at 9181 ARHGEF2 5.36 1.40E-06 7.05E-06 1.28E-03 2.255 1.356 1.865 2.523 2.23E-04 219045_at 54509 RHOF 5.26 2.73E-06 7.67E-06 1.33E-03 0.743 -0.045 1.727 2.141 2.11E-03 202806_at 1627 DBN1 4.91 8.73E-06 2.14E-05 2.05E-03 0.795 -0.277 2.102 1.567 1.07E-02 217838_s_at 51466 EVL 3.88 2.51E-04 4.42E-04 9.56E-03 1.548 0.700 1.801 1.307 2.50E-01 GO:0030334 (p=0.000151) regulation of cell migration 210150_s_at 3911 LAMA5 4.43 5.89E-05 7.11E-05 3.68E-03 0.600 -0.095 1.619 1.316 2.82E-01 209784_s_at 3714 JAG2 4.25 1.33E-04 1.04E-04 4.51E-03 0.234 -0.417 1.570 2.166 4.16E-03 216268_s_at 182 JAG1 4.23 7.73E-05 1.73E-04 5.92E-03 2.704 1.543 2.236 1.209 2.29E-01 202202_s_at 3910 LAMA4 4.00 1.72E-04 3.00E-04 7.88E-03 0.725 -0.058 1.720 1.381 1.00E-01 GO:0006096 (p=0.000286) Glycolysis 201037_at 5214 PFKP 5.23 3.40E-06 7.92E-06 1.35E-03 1.422 0.184 2.358 1.567 6.86E-03 201251_at 5315 PKM2 4.84 1.08E-05 2.66E-05 2.27E-03 2.833 1.384 2.730 1.466 4.09E-03 210976_s_at 5213 PFKM 4.35 5.06E-05 1.25E-04 4.93E-03 1.138 0.344 1.733 1.566 5.29E-02 202934_at 3099 HK2 4.24 1.07E-04 1.23E-04 4.87E-03 1.162 -0.298 2.751 1.283 1.45E-02 214687_x_at 226 ALDOA 3.99 1.95E-04 2.91E-04 7.68E-03 5.072 4.356 1.643 2.365 8.22E-04 220585_at 80201 HKDC1 3.80 3.47E-04 5.13E-04 1.04E-02 0.627 -0.352 1.971 1.664 2.96E-03 201313_at 2026 ENO2 3.46 1.36E-03 9.89E-04 1.46E-02 -0.597 -1.770 2.256 1.383 1.12E-03 GO:0007010 (p=0.000710) cytoskeleton organization and biogenesis 217733_s_at 9168 TMSB10 5.94 1.65E-07 2.11E-06 8.66E-04 6.719 5.692 2.038 1.555 6.00E-02 204992_s_at 5217 PFN2 5.38 1.59E-06 5.89E-06 1.20E-03 1.815 0.180 3.106 1.391 8.10E-03 204425_at 393 ARHGAP4 4.68 2.56E-05 3.50E-05 2.55E-03 -0.161 -0.663 1.416 2.634 1.89E-02 219901_at 55785 FGD6 4.57 2.56E-05 6.07E-05 3.45E-03 -0.107 -0.866 1.693 2.028 4.87E-03 218376_s_at 64780 MICAL1 4.40 7.32E-05 7.17E-05 3.69E-03 0.220 -0.590 1.753 1.568 4.73E-02 205120_s_at 6443 SGCB 4.36 5.09E-05 1.15E-04 4.78E-03 0.856 -0.303 2.233 1.276 1.57E-01 215028_at 57556 SEMA6A 4.19 1.45E-04 1.30E-04 5.05E-03 -1.738 -2.696 1.943 1.360 8.72E-02 205111_s_at 51196 PLCE1 3.67 5.45E-04 6.78E-04 1.19E-02 -0.689 -1.393 1.628 1.465 7.73E-02 GO:0007169 (p=0.000934) transmembrane receptor tyrosine kinase signaling pathway 202388_at 5997 RGS2 6.94 5.30E-09 1.10E-07 3.79E-04 3.198 1.073 4.361 1.683 4.20E-05 215446_s_at 4015 LOX 4.37 6.53E-05 8.67E-05 4.08E-03 0.375 -1.194 2.967 1.313 1.44E-02 210749_x_at 780 DDR1 4.26 6.98E-05 1.71E-04 5.90E-03 2.023 1.097 1.900 1.361 1.23E-01 203789_s_at 10512 SEMA3C 4.25 1.01E-04 1.17E-04 4.80E-03 -0.945 -2.522 2.984 1.239 6.51E-02 202404_s_at 1278 COL1A2 4.14 1.10E-04 2.08E-04 6.43E-03 3.980 2.236 3.349 1.172 1.66E-01 209283_at 1410 CRYAB 3.81 4.83E-04 3.71E-04 8.72E-03 0.871 -0.481 2.553 1.157 2.24E-01 206074_s_at 3159 HMGA1 3.77 3.70E-04 6.85E-04 1.20E-02 2.113 1.361 1.685 1.625 2.31E-02 206070_s_at 2042 EPHA3 3.57 8.52E-04 7.93E-04 1.31E-02 -0.640 -1.891 2.380 1.106 4.55E-01 GO:0001709 (p=0.000999) cell fate determination 209784_s_at 3714 JAG2 4.25 1.33E-04 1.04E-04 4.51E-03 0.234 -0.417 1.570 2.166 4.16E-03 216268_s_at 182 JAG1 4.23 7.73E-05 1.73E-04 5.92E-03 2.704 1.543 2.236 1.209 2.29E-01 212377_s_at 4853 NOTCH2 3.91 2.26E-04 4.30E-04 9.40E-03 3.141 2.505 1.554 1.372 2.02E-01 GO:0001501 (p=0.001675) skeletal development 210809_s_at 10631 POSTN 4.98 5.57E-06 2.03E-05 2.01E-03 2.676 0.221 5.487 1.190 6.54E-02 202404_s_at 1278 COL1A2 4.14 1.10E-04 2.08E-04 6.43E-03 3.980 2.236 3.349 1.172 1.66E-01 201995_at 2131 EXT1 4.13 1.25E-04 1.91E-04 6.25E-03 4.043 3.312 1.660 1.652 9.33E-02 202310_s_at 1277 COL1A1 3.75 3.98E-04 5.96E-04 1.12E-02 3.090 1.432 3.155 1.146 2.28E-01 41037_at 7004 TEAD4 3.73 4.73E-04 5.54E-04 1.08E-02 -1.332 -2.001 1.590 1.473 7.74E-02 202935_s_at 6662 SOX9 3.71 4.39E-04 7.39E-04 1.25E-02 1.737 -0.071 3.501 1.020 8.22E-01 213622_at 1298 COL9A2 3.53 1.28E-03 7.47E-04 1.26E-02 -0.624 -1.201 1.491 1.482 8.33E-02 211535_s_at 2260 FGFR1 3.47 1.22E-03 9.97E-04 1.46E-02 0.861 0.171 1.614 1.534 1.67E-02 GO:0007399 (p=0.002294) neurogenesis 209897_s_at 9353 SLIT2 4.96 1.40E-05 1.40E-05 1.66E-03 -0.147 -1.219 2.102 1.485 3.03E-02 202806_at 1627 DBN1 4.91 8.73E-06 2.14E-05 2.05E-03 0.795 -0.277 2.102 1.567 1.07E-02 213746_s_at 2316 FLNA 4.23 1.16E-04 1.20E-04 4.84E-03 1.489 0.502 1.983 1.572 2.27E-02 204470_at 2919 CXCL1 4.36 8.12E-05 8.26E-05 3.97E-03 -0.831 -2.276 2.721 1.236 4.63E-02 200975_at 5538 PPT1 4.31 6.57E-05 1.16E-04 4.79E-03 4.197 3.662 1.450 3.346 4.96E-04 216268_s_at 182 JAG1 4.23 7.73E-05 1.73E-04 5.92E-03 2.704 1.543 2.236 1.209 2.29E-01 215028_at 57556 SEMA6A 4.19 1.45E-04 1.30E-04 5.05E-03 -1.738 -2.696 1.943 1.360 8.72E-02 210302_s_at 10586 MAB21L2 4.01 2.30E-04 2.27E-04 6.72E-03 -1.198 -2.228 2.041 1.361 5.49E-02 212377_s_at 4853 NOTCH2 3.91 2.26E-04 4.30E-04 9.40E-03 3.141 2.505 1.554 1.372 2.02E-01 217838_s_at 51466 EVL 3.88 2.51E-04 4.42E-04 9.56E-03 1.548 0.700 1.801 1.307 2.50E-01 203603_s_at 9839 ZFHX1B 3.82 3.70E-04 4.16E-04 9.21E-03 -1.317 -2.101 1.722 1.800 6.84E-03 200762_at 1808 DPYSL2 3.82 3.33E-04 4.69E-04 9.83E-03 3.168 2.386 1.720 2.099 2.93E-03 209199_s_at 4208 MEF2C 3.68 4.82E-04 7.58E-04 1.27E-02 1.651 1.133 1.433 2.156 2.10E-02 202192_s_at 8522 GAS7 3.63 8.42E-04 6.23E-04 1.15E-02 0.070 -0.492 1.476 1.965 3.30E-03 219049_at 55790 ChGn 3.59 7.08E-04 8.55E-04 1.36E-02 0.067 -0.517 1.498 1.528 1.27E-01 201431_s_at 1809 DPYSL3 3.55 9.36E-04 8.28E-04 1.34E-02 0.431 -0.527 1.944 1.257 1.96E-01 GO:0008283 (p=0.002568) cell proliferation 204984_at 2239 GPC4 6.12 1.63E-07 7.37E-07 6.84E-04 -0.548 -1.844 2.454 1.252 1.64E-01 203683_s_at 7423 VEGFB 5.59 5.29E-07 4.64E-06 1.12E-03 0.834 -0.059 1.858 2.046 1.57E-02 200972_at 10099 TSPAN3 5.43 1.31E-06 5.19E-06 1.13E-03 3.941 3.032 1.878 1.844 2.30E-03 221530_s_at 79365 BHLHB3 5.05 7.23E-06 1.26E-05 1.61E-03 -0.059 -1.547 2.807 1.422 8.16E-03 201280_s_at 1601 DAB2 5.03 5.40E-06 1.52E-05 1.72E-03 2.887 1.529 2.564 1.631 2.42E-03 217728_at 6277 S100A6 5.03 6.66E-06 1.42E-05 1.67E-03 2.704 1.092 3.057 1.338 2.60E-02 203085_s_at 7040 TGFB1 4.39 5.96E-05 8.25E-05 3.97E-03 1.581 0.368 2.320 1.449 1.22E-02 204470_at 2919 CXCL1 4.36 8.12E-05 8.26E-05 3.97E-03 -0.831 -2.276 2.721 1.236 4.63E-02 205463_s_at 5154 PDGFA 4.00 1.74E-04 3.17E-04 8.08E-03 0.890 -0.172 2.087 1.154 3.94E-01 202286_s_at 4070 TACSTD2 3.96 3.00E-04 2.44E-04 6.97E-03 -0.657 -1.917 2.395 1.347 5.55E-03 205569_at 27074 LAMP3 3.95 2.19E-04 3.32E-04 8.22E-03 -0.725 -1.558 1.782 1.473 6.01E-02 208884_s_at 51366 EDD1 3.94 2.08E-04 3.83E-04 8.85E-03 2.926 2.339 1.502 1.200 5.41E-01 205081_at 1396 CRIP1 3.77 3.88E-04 5.48E-04 1.07E-02 0.378 -0.513 1.856 1.201 3.30E-01 205111_s_at 51196 PLCE1 3.67 5.45E-04 6.78E-04 1.19E-02 -0.689 -1.393 1.628 1.465 7.73E-02 219049_at 55790 ChGn 3.59 7.08E-04 8.55E-04 1.36E-02 0.067 -0.517 1.498 1.528 1.27E-01 209909_s_at 7042 TGFB2 3.48 1.23E-03 9.62E-04 1.44E-02 -2.046 -2.889 1.794 1.176 3.24E-01 GO:0000074 (p=0.002612) regulation of progression through cell cycle 203683_s_at 7423 VEGFB 5.59 5.29E-07 4.64E-06 1.12E-03 0.834 -0.059 1.858 2.046 1.57E-02 217728_at 6277 S100A6 5.03 6.66E-06 1.42E-05 1.67E-03 2.704 1.092 3.057 1.338 2.60E-02 211921_x_at 5757 PTMA 4.73 1.52E-05 3.71E-05 2.63E-03 5.227 4.673 1.468 1.928 8.12E-02 203693_s_at 1871 E2F3 4.48 3.67E-05 1.07E-04 4.64E-03 0.973 0.024 1.930 1.509 4.99E-02 208656_s_at 10983 CCNI 4.48 4.54E-05 6.51E-05 3.55E-03 4.443 3.906 1.451 3.251 3.88E-03 203085_s_at 7040 TGFB1 4.39 5.96E-05 8.25E-05 3.97E-03 1.581 0.368 2.320 1.449 1.22E-02 203685_at 596 BCL2 4.33 6.34E-05 1.09E-04 4.67E-03 -0.251 -1.056 1.747 1.300 2.77E-01 202934_at 3099 HK2 4.24 1.07E-04 1.23E-04 4.87E-03 1.162 -0.298 2.751 1.283 1.45E-02 201700_at 896 CCND3 4.08 1.89E-04 1.86E-04 6.16E-03 2.012 1.416 1.511 3.033 1.73E-05 200953_s_at 894 CCND2 4.00 2.01E-04 2.60E-04 7.24E-03 0.703 -0.200 1.870 1.152 4.50E-01 205463_s_at 5154 PDGFA 4.00 1.74E-04 3.17E-04 8.08E-03 0.890 -0.172 2.087 1.154 3.94E-01 204014_at 1846 DUSP4 3.77 6.62E-04 3.73E-04 8.73E-03 -1.469 -2.526 2.081 1.384 1.56E-02 201482_at 5768 QSCN6 3.80 3.91E-04 4.53E-04 9.69E-03 1.460 0.388 2.102 1.257 1.10E-01 209909_s_at 7042 TGFB2 3.48 1.23E-03 9.62E-04 1.44E-02 -2.046 -2.889 1.794 1.176 3.24E-01 GO:0006935 (p=0.002643) chemotaxis 209897_s_at 9353 SLIT2 4.96 1.40E-05 1.40E-05 1.66E-03 -0.147 -1.219 2.102 1.485 3.03E-02 202859_x_at 3576 IL8 4.51 3.21E-05 6.95E-05 3.63E-03 1.804 -0.055 3.629 1.245 1.64E-02 206336_at 6372 CXCL6 4.39 8.73E-05 6.90E-05 3.63E-03 -0.798 -2.716 3.780 1.251 1.96E-02 204470_at 2919 CXCL1 4.36 8.12E-05 8.26E-05 3.97E-03 -0.831 -2.276 2.721 1.236 4.63E-02 205479_s_at 5328 PLAU 4.10 1.95E-04 1.64E-04 5.74E-03 0.516 -0.249 1.699 1.965 4.85E-04 209392_at 5168 ENPP2 3.70 4.92E-04 8.87E-04 1.39E-02 4.249 3.262 1.981 1.140 3.76E-01 205206_at 3730 KAL1 3.67 6.34E-04 5.94E-04 1.12E-02 -0.824 -1.747 1.896 1.284 1.55E-01 216598_s_at 6347 CCL2 3.67 6.20E-04 6.31E-04 1.15E-02 1.659 0.516 2.209 1.387 6.11E-02 210845_s_at 5329 PLAUR 3.51 1.04E-03 9.40E-04 1.42E-02 0.454 -0.455 1.877 1.569 1.31E-03 GO:0016049 (p=0.003039) cell growth 203085_s_at 7040 TGFB1 4.39 5.96E-05 8.25E-05 3.97E-03 1.581 0.368 2.320 1.449 1.22E-02 203638_s_at 2263 FGFR2 4.36 5.49E-05 1.47E-04 5.41E-03 3.195 0.907 4.885 1.132 1.38E-01 212377_s_at 4853 NOTCH2 3.91 2.26E-04 4.30E-04 9.40E-03 3.141 2.505 1.554 1.372 2.02E-01 209909_s_at 7042 TGFB2 3.48 1.23E-03 9.62E-04 1.44E-02 -2.046 -2.889 1.794 1.176 3.24E-01 211535_s_at 2260 FGFR1 3.47 1.22E-03 9.97E-04 1.46E-02 0.861 0.171 1.614 1.534 1.67E-02 GO:0006928 (p=0.003379) cell motility 200972_at 10099 TSPAN3 5.43 1.31E-06 5.19E-06 1.13E-03 3.941 3.032 1.878 1.844 2.30E-03 213746_s_at 2316 FLNA 4.23 1.16E-04 1.20E-04 4.84E-03 1.489 0.502 1.983 1.572 2.27E-02 202859_x_at 3576 IL8 4.51 3.21E-05 6.95E-05 3.63E-03 1.804 -0.055 3.629 1.245 1.64E-02 201670_s_at 4082 MARCKS 4.31 5.86E-05 1.30E-04 5.06E-03 2.917 1.979 1.916 1.427 7.03E-02 209101_at 1490 CTGF 3.88 2.87E-04 3.70E-04 8.72E-03 3.036 1.832 2.304 1.273 1.60E-01 203476_at 7162 TPBG 3.85 3.51E-04 3.73E-04 8.73E-03 0.208 -0.983 2.282 1.307 1.86E-02 209392_at 5168 ENPP2 3.70 4.92E-04 8.87E-04 1.39E-02 4.249 3.262 1.981 1.140 3.76E-01 205206_at 3730 KAL1 3.67 6.34E-04 5.94E-04 1.12E-02 -0.824 -1.747 1.896 1.284 1.55E-01 210845_s_at 5329 PLAUR 3.51 1.04E-03 9.40E-04 1.42E-02 0.454 -0.455 1.877 1.569 1.31E-03 GO:0007166 (p=0.004334) cell surface receptor linked signal transduction 209435_s_at 9181 ARHGEF2 5.36 1.40E-06 7.05E-06 1.28E-03 2.255 1.356 1.865 2.523 2.23E-04 204451_at 8321 FZD1 4.81 1.98E-05 2.24E-05 2.08E-03 0.197 -0.807 2.005 1.391 3.67E-02 213746_s_at 2316 FLNA 4.23 1.16E-04 1.20E-04 4.84E-03 1.489 0.502 1.983 1.572 2.27E-02 215028_at 57556 SEMA6A 4.19 1.45E-04 1.30E-04 5.05E-03 -1.738 -2.696 1.943 1.360 8.72E-02 205463_s_at 5154 PDGFA 4.00 1.74E-04 3.17E-04 8.08E-03 0.890 -0.172 2.087 1.154 3.94E-01 204472_at 2669 GEM 3.99 1.81E-04 3.06E-04 7.93E-03 1.407 0.016 2.621 1.257 8.42E-02 202286_s_at 4070 TACSTD2 3.96 3.00E-04 2.44E-04 6.97E-03 -0.657 -1.917 2.395 1.347 5.55E-03 219423_x_at 8718 TNFRSF25 3.96 2.18E-04 3.01E-04 7.88E-03 -0.964 -1.532 1.482 1.534 1.26E-01 217838_s_at 51466 EVL 3.88 2.51E-04 4.42E-04 9.56E-03 1.548 0.700 1.801 1.307 2.50E-01 210845_s_at 5329 PLAUR 3.51 1.04E-03 9.40E-04 1.42E-02 0.454 -0.455 1.877 1.569 1.31E-03 GO:0006974 (p=0.004615) response to DNA damage stimulus 212997_s_at 11011 TLK2 4.15 1.05E-04 1.99E-04 6.29E-03 0.891 0.379 1.426 2.066 3.96E-02 208884_s_at 51366 EDD1 3.94 2.08E-04 3.83E-04 8.85E-03 2.926 2.339 1.502 1.200 5.41E-01 209383_at 1649 DDIT3 3.85 3.92E-04 3.50E-04 8.50E-03 2.755 2.116 1.558 2.220 5.12E-03 GO:0030155 (p=0.004615) regulation of cell adhesion 202859_x_at 3576 IL8 4.51 3.21E-05 6.95E-05 3.63E-03 1.804 -0.055 3.629 1.245 1.64E-02 210150_s_at 3911 LAMA5 4.43 5.89E-05 7.11E-05 3.68E-03 0.600 -0.095 1.619 1.316 2.82E-01 202202_s_at 3910 LAMA4 4.00 1.72E-04 3.00E-04 7.88E-03 0.725 -0.058 1.720 1.381 1.00E-01 GO:0007605 (p=0.004789) perception of sound 210139_s_at 5376 PMP22 4.67 2.36E-05 3.74E-05 2.63E-03 1.773 0.501 2.414 1.510 1.35E-02 37892_at 1301 COL11A1 4.63 5.43E-05 3.20E-05 2.43E-03 -1.368 -2.784 2.668 1.449 2.03E-03 209784_s_at 3714 JAG2 4.25 1.33E-04 1.04E-04 4.51E-03 0.234 -0.417 1.570 2.166 4.16E-03 205427_at 6940 ZNF354A 4.25 8.20E-05 2.03E-04 6.39E-03 0.438 -0.417 1.810 1.191 4.28E-01 203215_s_at 4646 MYO6 4.17 9.79E-05 1.95E-04 6.25E-03 0.616 -0.115 1.660 1.875 3.75E-03 202404_s_at 1278 COL1A2 4.14 1.10E-04 2.08E-04 6.43E-03 3.980 2.236 3.349 1.172 1.66E-01 202291_s_at 4256 MGP 3.84 2.98E-04 4.61E-04 9.79E-03 2.896 1.166 3.316 1.080 4.31E-01 202310_s_at 1277 COL1A1 3.75 3.98E-04 5.96E-04 1.12E-02 3.090 1.432 3.155 1.146 2.28E-01 GO:0007517 (p=0.005048) muscle development 219833_s_at 114327 EFHC1 4.88 7.45E-06 2.98E-05 2.35E-03 0.420 -0.310 1.659 1.656 3.57E-02 204083_s_at 7169 TPM2 4.61 2.44E-05 5.00E-05 3.07E-03 1.491 0.324 2.244 1.367 9.72E-02 201818_at 79888 AYTL2 4.37 4.82E-05 1.11E-04 4.74E-03 1.529 0.567 1.948 1.424 4.59E-02 205120_s_at 6443 SGCB 4.36 5.09E-05 1.15E-04 4.78E-03 0.856 -0.303 2.233 1.276 1.57E-01 201438_at 1293 COL6A3 4.12 1.29E-04 1.94E-04 6.25E-03 2.511 1.159 2.553 1.215 1.58E-01 206106_at 6300 MAPK12 4.06 2.22E-04 1.85E-04 6.14E-03 -0.818 -1.521 1.628 1.398 1.71E-01 41037_at 7004 TEAD4 3.73 4.73E-04 5.54E-04 1.08E-02 -1.332 -2.001 1.590 1.473 7.74E-02 209199_s_at 4208 MEF2C 3.68 4.82E-04 7.58E-04 1.27E-02 1.651 1.133 1.433 2.156 2.10E-02 209344_at 7171 TPM4 3.64 5.47E-04 8.98E-04 1.39E-02 0.857 0.185 1.594 1.245 3.06E-01 GO:0001558 (p=0.005518) regulation of cell growth 203683_s_at 7423 VEGFB 5.59 5.29E-07 4.64E-06 1.12E-03 0.834 -0.059 1.858 2.046 1.57E-02 210095_s_at 3486 IGFBP3 4.30 6.42E-05 1.32E-04 5.09E-03 4.880 3.765 2.167 1.824 9.23E-04 209101_at 1490 CTGF 3.88 2.87E-04 3.70E-04 8.72E-03 3.036 1.832 2.304 1.273 1.60E-01 210095_s_at 3486 IGFBP3 4.30 6.42E-05 1.32E-04 5.09E-03 4.880 3.765 2.167 1.824 9.23E-04 201482_at 5768 QSCN6 3.80 3.91E-04 4.53E-04 9.69E-03 1.460 0.388 2.102 1.257 1.10E-01 205111_s_at 51196 PLCE1 3.67 5.45E-04 6.78E-04 1.19E-02 -0.689 -1.393 1.628 1.465 7.73E-02 210001_s_at 8651 SOCS1 3.66 6.54E-04 6.19E-04 1.14E-02 -0.101 -0.761 1.580 1.623 5.31E-02 GO:0009968 (p=0.007379) negative regulation of signal transduction 202388_at 5997 RGS2 6.94 5.30E-09 1.10E-07 3.79E-04 3.198 1.073 4.361 1.683 4.20E-05 216834_at 5996 RGS1 5.56 5.86E-07 4.95E-06 1.13E-03 3.288 1.540 3.359 1.570 1.69E-03 204319_s_at 6001 RGS10 4.62 1.92E-05 5.80E-05 3.38E-03 1.652 0.709 1.922 1.804 7.25E-03 210095_s_at 3486 IGFBP3 4.30 6.42E-05 1.32E-04 5.09E-03 4.880 3.765 2.167 1.824 9.23E-04 GO:0007050 (p=0.007602) cell cycle arrest 202859_x_at 3576 IL8 4.51 3.21E-05 6.95E-05 3.63E-03 1.804 -0.055 3.629 1.245 1.64E-02 206106_at 6300 MAPK12 4.06 2.22E-04 1.85E-04 6.14E-03 -0.818 -1.521 1.628 1.398 1.71E-01 209318_x_at 5325 PLAGL1 3.96 2.10E-04 3.16E-04 8.06E-03 -0.260 -1.630 2.585 1.427 6.33E-03 212377_s_at 4853 NOTCH2 3.91 2.26E-04 4.30E-04 9.40E-03 3.141 2.505 1.554 1.372 2.02E-01 209383_at 1649 DDIT3 3.85 3.92E-04 3.50E-04 8.50E-03 2.755 2.116 1.558 2.220 5.12E-03 202192_s_at 8522 GAS7 3.63 8.42E-04 6.23E-04 1.15E-02 0.070 -0.492 1.476 1.965 3.30E-03 GO:0006959 (p=0.008336) humoral immune response 208650_s_at 934 CD24 5.42 2.99E-06 1.11E-05 1.52E-03 3.937 1.162 6.844 1.046 5.50E-01 203685_at 596 BCL2 4.33 6.34E-05 1.09E-04 4.67E-03 -0.251 -1.056 1.747 1.300 2.77E-01 219725_at 54209 TREM2 4.05 1.77E-04 2.18E-04 6.57E-03 0.741 -0.024 1.699 1.849 3.78E-03 216598_s_at 6347 CCL2 3.67 6.20E-04 6.31E-04 1.15E-02 1.659 0.516 2.209 1.387 6.11E-02 Down-regulated genes Entrez Gene T- P-value, Low- Fold P- Probe ID Symbol P-value FDR High-risk HR ID statistic permuted risk difference value GO:0006629 (p=0.000000) lipid metabolism 212230_at 8613 PPAP2B -4.28 6.82E-05 1.41E-04 5.29E-03 2.430 3.129 0.616 0.592 4.16E-02 217173_s_at 3949 LDLR -3.88 2.78E-04 3.97E-04 9.00E-03 -0.125 0.535 0.633 0.719 1.99E-01 205675_at 4547 MTTP -3.82 4.07E-04 3.97E-04 9.00E-03 2.089 3.663 0.336 0.784 1.14E-02 202054_s_at 224 ALDH3A2 -3.97 1.97E-04 3.29E-04 8.22E-03 4.174 4.905 0.603 0.520 1.91E-02 209759_s_at 1632 DCI -4.29 7.20E-05 1.19E-04 4.84E-03 2.313 2.932 0.651 0.370 9.46E-04 205364_at 8309 ACOX2 -4.32 1.09E-04 8.40E-05 4.00E-03 2.945 4.289 0.394 0.751 1.55E-02 207601_at 27284 SULT1B1 -4.40 5.92E-05 1.49E-04 5.44E-03 -1.134 -0.074 0.480 0.755 1.38E-01 206738_at 346 APOC4 -4.49 4.28E-05 6.42E-05 3.53E-03 2.432 4.391 0.257 0.801 1.20E-02 205913_at 5346 PLIN -4.51 3.10E-05 9.34E-05 4.24E-03 -0.538 0.376 0.531 0.564 1.40E-02 206870_at 5465 PPARA -4.53 3.44E-05 6.03E-05 3.45E-03 -0.278 0.588 0.548 0.703 1.61E-01 205355_at 36 ACADSB -4.61 3.25E-05 4.23E-05 2.81E-03 1.009 2.227 0.430 0.768 8.96E-02 210614_at 7274 TTPA -4.64 1.95E-05 5.02E-05 3.08E-03 -0.193 1.207 0.379 0.820 1.35E-01 202025_x_at 30 ACAA1 -5.29 2.06E-06 7.86E-06 1.35E-03 2.604 3.485 0.543 0.597 3.57E-02 220753_s_at 51084 CRYL1 -4.84 1.37E-05 2.34E-05 2.15E-03 2.524 3.745 0.429 0.543 5.21E-05 216889_s_at 3172 HNF4A -5.33 1.43E-06 8.86E-06 1.40E-03 -0.055 0.595 0.637 0.341 2.95E-03 201135_at 1892 ECHS1 -4.89 8.32E-06 2.46E-05 2.20E-03 4.763 5.420 0.634 0.522 4.26E-02 206293_at 6822 SULT2A1 -4.94 1.63E-05 1.43E-05 1.68E-03 3.016 4.703 0.310 0.725 1.56E-03 209522_s_at 1384 CRAT -5.09 4.54E-06 1.26E-05 1.61E-03 2.205 2.815 0.655 0.248 1.08E-04 201413_at 3295 HSD17B4 -5.46 1.31E-06 4.53E-06 1.12E-03 4.600 5.334 0.602 0.436 5.28E-03 218322_s_at 51703 ACSL5 -5.62 5.26E-07 3.49E-06 1.05E-03 1.254 2.723 0.361 0.577 6.07E-04 207621_s_at 10400 PEMT -6.68 9.09E-09 2.32E-07 5.17E-04 1.564 3.022 0.364 0.567 2.84E-03 GO:0006118 (p=0.000002) electron transport 206878_at 1610 DAO -3.60 6.88E-04 8.28E-04 1.34E-02 0.575 1.987 0.376 0.780 2.74E-02 221605_s_at 51268 PIPOX -3.61 7.28E-04 7.48E-04 1.26E-02 4.049 5.135 0.471 0.769 3.99E-02 210452_x_at 8529 CYP4F2 -3.65 6.57E-04 6.58E-04 1.17E-02 1.869 3.370 0.353 0.816 4.45E-02 206515_at 4051 CYP4F3 -4.32 8.97E-05 9.42E-05 4.26E-03 2.593 4.086 0.355 0.774 1.81E-02 206263_at 2329 FMO4 -3.99 1.92E-04 2.82E-04 7.59E-03 1.225 2.318 0.469 0.673 1.33E-02 201432_at 847 CAT -4.00 2.36E-04 2.34E-04 6.79E-03 5.841 6.582 0.598 0.664 6.26E-02 214829_at 10157 AASS -4.01 1.74E-04 3.71E-04 8.72E-03 -1.393 -0.351 0.486 0.799 1.78E-01 214420_s_at 1559 CYP2C9 -4.33 5.49E-05 1.23E-04 4.87E-03 0.250 1.302 0.482 0.767 1.17E-01 210862_s_at 1757 SARDH -4.85 8.71E-06 3.00E-05 2.35E-03 -0.743 0.307 0.483 0.681 5.39E-02 204067_at 6821 SUOX -4.26 7.28E-05 1.41E-04 5.29E-03 1.681 2.321 0.642 0.527 3.11E-02 211441_x_at 64816 CYP3A43 -4.41 4.23E-05 1.16E-04 4.79E-03 -0.037 1.050 0.471 0.645 1.21E-02 209366_x_at 1528 CYB5A -4.70 2.75E-05 3.07E-05 2.38E-03 5.643 6.511 0.548 0.589 4.78E-03 205364_at 8309 ACOX2 -4.32 1.09E-04 8.40E-05 4.00E-03 2.945 4.289 0.394 0.751 1.55E-02 205355_at 36 ACADSB -4.61 3.25E-05 4.23E-05 2.81E-03 1.009 2.227 0.430 0.768 8.96E-02 205073_at 1573 CYP2J2 -4.67 3.60E-05 3.20E-05 2.43E-03 1.733 3.317 0.333 0.697 1.21E-03 206539_s_at 66002 CYP4F12 -4.86 9.48E-06 2.61E-05 2.24E-03 1.368 2.145 0.583 0.406 1.34E-03 209975_at 1571 CYP2E1 -4.87 9.51E-06 2.45E-05 2.20E-03 2.911 6.318 0.094 0.886 2.33E-02 208369_s_at 2639 GCDH -5.16 2.80E-06 1.52E-05 1.72E-03 1.364 2.402 0.487 0.841 3.90E-01 219418_at 79840 XLF -5.43 9.56E-07 6.74E-06 1.25E-03 -0.030 0.510 0.688 0.304 3.00E-03 203979_at 1593 CYP27A1 -5.53 1.49E-06 3.35E-06 1.05E-03 4.124 5.323 0.436 0.530 2.28E-04 221941_at 196743 PAOX -6.09 8.51E-08 1.02E-06 7.79E-04 0.297 0.857 0.678 0.580 2.30E-01 208928_at 5447 POR -6.36 3.72E-08 4.72E-07 6.19E-04 2.866 4.158 0.408 0.605 5.98E-03 GO:0006520 (p=0.000008) amino acid metabolism 202740_at 95 ACY1 -3.65 6.83E-04 6.53E-04 1.17E-02 3.619 4.545 0.526 0.747 7.64E-02 200708_at 2806 GOT2 -3.68 5.15E-04 7.12E-04 1.23E-02 3.802 4.561 0.591 0.584 1.12E-02 218653_at 10166 SLC25A15 -3.78 3.51E-04 5.71E-04 1.09E-02 2.626 3.764 0.455 0.722 3.80E-02 200946_x_at 2746 GLUD1 -3.99 1.77E-04 3.11E-04 8.01E-03 3.953 4.974 0.493 0.729 3.22E-02 215794_x_at 2747 GLUD2 -3.97 1.89E-04 3.31E-04 8.22E-03 2.933 4.009 0.474 0.744 3.81E-02 221139_s_at 51380 CSAD -4.11 1.24E-04 2.83E-04 7.59E-03 0.862 1.710 0.555 0.737 1.40E-01 209123_at 5860 QDPR -4.34 6.71E-05 1.01E-04 4.48E-03 3.936 4.862 0.526 0.768 1.87E-01 205813_s_at 4143 MAT1A -4.61 4.71E-05 3.69E-05 2.62E-03 3.998 5.452 0.365 0.793 5.11E-02 GO:0006559 (p=0.000016) L-phenylalanine catabolism 217583_at 5053 PAH -3.80 5.05E-04 3.74E-04 8.73E-03 1.110 2.617 0.352 0.730 3.44E-03 214307_at 3081 HGD -4.26 7.96E-05 1.30E-04 5.05E-03 2.474 3.636 0.447 0.804 1.45E-01 209123_at 5860 QDPR -4.34 6.71E-05 1.01E-04 4.48E-03 3.936 4.862 0.526 0.768 1.87E-01 206024_at 3242 HPD -4.53 4.23E-05 5.28E-05 3.18E-03 2.184 5.176 0.126 0.880 5.60E-02 GO:0006069 (p=0.000071) ethanol oxidation 208848_at 128 ADH5 -3.75 4.54E-04 5.25E-04 1.05E-02 2.930 3.689 0.591 0.536 6.25E-03 209612_s_at 125 ADH1B -4.74 3.05E-05 2.58E-05 2.24E-03 4.131 6.468 0.198 0.794 1.38E-03 207544_s_at 130 ADH6 -5.70 8.54E-07 2.06E-06 8.66E-04 0.967 3.092 0.229 0.670 2.29E-04 GO:0009636 (p=0.001078) response to toxin 202017_at 2052 EPHX1 -3.69 6.56E-04 5.41E-04 1.07E-02 6.135 7.071 0.522 0.719 3.93E-02 209368_at 2053 EPHX2 -3.89 2.58E-04 3.91E-04 8.93E-03 1.869 3.056 0.439 0.614 8.13E-04 205750_at 670 BPHL -6.08 1.11E-07 9.46E-07 7.79E-04 2.214 3.141 0.526 0.447 2.53E-03 GO:0006869 (p=0.001175) lipid transport 205820_s_at 345 APOC3 -3.49 1.40E-03 8.57E-04 1.36E-02 6.454 7.737 0.411 0.759 2.59E-03 219716_at 80830 APOL6 -3.59 6.58E-04 9.19E-04 1.41E-02 1.668 2.341 0.627 0.709 1.44E-01 217173_s_at 3949 LDLR -3.88 2.78E-04 3.97E-04 9.00E-03 -0.125 0.535 0.633 0.719 1.99E-01 205675_at 4547 MTTP -3.82 4.07E-04 3.97E-04 9.00E-03 2.089 3.663 0.336 0.784 1.14E-02 218676_s_at 58488 PCTP -4.16 1.24E-04 1.63E-04 5.73E-03 2.475 3.251 0.584 0.706 1.26E-01 206738_at 346 APOC4 -4.49 4.28E-05 6.42E-05 3.53E-03 2.432 4.391 0.257 0.801 1.20E-02 GO:0006958 (p=0.001743) complement activation, classical pathway 200986_at 710 SERPING1 -3.60 8.29E-04 7.27E-04 1.24E-02 5.097 5.966 0.547 0.781 1.42E-01 205654_at 722 C4BPA -3.89 4.11E-04 2.84E-04 7.62E-03 4.860 6.465 0.329 0.778 4.32E-03 207041_at 10747 MASP2 -5.26 2.67E-06 7.97E-06 1.35E-03 0.267 2.179 0.266 0.789 1.76E-02 208209_s_at 725 C4BPB -4.29 1.04E-04 9.67E-05 4.32E-03 3.726 4.854 0.457 0.684 4.64E-03 GO:0006094 (p=0.001815) gluconeogenesis 202847_at 5106 PCK2 -3.61 6.12E-04 9.36E-04 1.42E-02 3.030 3.912 0.543 0.785 1.41E-01 206709_x_at 2875 GPT -3.66 5.25E-04 7.75E-04 1.29E-02 1.094 1.629 0.690 0.724 2.79E-01 204476_s_at 5091 PC -4.63 2.89E-05 4.03E-05 2.74E-03 2.213 3.229 0.495 0.721 6.66E-02 GO:0006807 (p=0.002277) nitrogen compound metabolism 206709_x_at 2875 GPT -3.66 5.25E-04 7.75E-04 1.29E-02 1.094 1.629 0.690 0.724 2.79E-01 204920_at 1373 CPS1 -3.73 5.95E-04 4.77E-04 9.95E-03 3.601 5.820 0.215 0.875 7.63E-02 217202_s_at 2752 GLUL -3.85 3.50E-04 6.56E-04 1.17E-02 3.820 5.086 0.416 0.725 3.87E-02 GO:0006805 (p=0.002600) xenobiotic metabolism 202017_at 2052 EPHX1 -3.69 6.56E-04 5.41E-04 1.07E-02 6.135 7.071 0.522 0.719 3.93E-02 209368_at 2053 EPHX2 -3.89 2.58E-04 3.91E-04 8.93E-03 1.869 3.056 0.439 0.614 8.13E-04 206263_at 2329 FMO4 -3.99 1.92E-04 2.82E-04 7.59E-03 1.225 2.318 0.469 0.673 1.33E-02 211441_x_at 64816 CYP3A43 -4.41 4.23E-05 1.16E-04 4.79E-03 -0.037 1.050 0.471 0.645 1.21E-02 GO:0006730 (p=0.002940) one-carbon compound metabolism 205208_at 10840 ALDH1L1 -3.94 2.24E-04 3.35E-04 8.23E-03 1.688 3.575 0.270 0.879 1.21E-01 219464_at 23632 CA14 -4.20 9.23E-05 2.22E-04 6.62E-03 -0.965 -0.160 0.572 0.472 6.28E-03 205813_s_at 4143 MAT1A -4.61 4.71E-05 3.69E-05 2.62E-03 3.998 5.452 0.365 0.793 5.11E-02 207421_at 763 CA5A -8.15 2.64E-11 8.99E-09 2.00E-04 -0.502 1.322 0.283 0.534 3.84E-04 GO:0008643 (p=0.004820) carbohydrate transport 207439_s_at 7355 SLC35A2 -3.66 5.58E-04 7.16E-04 1.23E-02 -0.256 0.284 0.688 0.552 7.46E-02 219991_at 56606 SLC2A9 -3.88 2.66E-04 5.26E-04 1.05E-02 -0.482 0.642 0.459 0.896 4.55E-01 206535_at 6514 SLC2A2 -4.51 7.39E-05 4.61E-05 2.98E-03 3.981 5.908 0.263 0.778 3.12E-03 GO:0009058 (p=0.004978) biosynthesis 206709_x_at 2875 GPT -3.66 5.25E-04 7.75E-04 1.29E-02 1.094 1.629 0.690 0.724 2.79E-01 200708_at 2806 GOT2 -3.68 5.15E-04 7.12E-04 1.23E-02 3.802 4.561 0.591 0.584 1.12E-02 205208_at 10840 ALDH1L1 -3.94 2.24E-04 3.35E-04 8.23E-03 1.688 3.575 0.270 0.879 1.21E-01 205633_s_at 211 ALAS1 -4.41 5.70E-05 7.83E-05 3.85E-03 3.452 4.597 0.452 0.830 2.42E-01 209577_at 5833 PCYT2 -4.91 6.89E-06 2.68E-05 2.27E-03 1.831 2.522 0.619 0.757 3.77E-01 GO:0006006 (p=0.005642) glucose metabolism 206952_at 2538 G6PC -3.56 9.00E-04 8.28E-04 1.34E-02 1.348 2.951 0.329 0.790 7.54E-03 202847_at 5106 PCK2 -3.61 6.12E-04 9.36E-04 1.42E-02 3.030 3.912 0.543 0.785 1.41E-01 217973_at 51181 DCXR -4.95 6.10E-06 2.21E-05 2.06E-03 4.591 5.986 0.380 0.801 1.25E-01 Abbreviations: FDR, false discovery rate; HR, hazard rate.

Supplementary Table 3. Comparison of CD24 expression levels between high- and low-risk groups of early recurrence in SNU dataset

Mean Mean P-value P-value Log- Fold Probe ID FDR (high-risk, (low-risk, (t-test) (permuted) ratio difference n = 31) n = 34) 208650_s_at 2.99E-06 1.11E-05 0.002 3.937 1.162 2.775 6.844 216379_x_at 2.41E-06 9.14E-06 0.001 5.849 3.100 2.749 6.721 209771_x_at 2.28E-06 8.63E-06 0.001 5.820 3.117 2.703 6.510 266_s_at 1.86E-06 7.72E-06 0.001 3.452 0.852 2.600 6.062 208651_x_at 9.20E-07 4.70E-06 0.001 3.049 0.732 2.317 4.984 209772_s_at 5.07E-06 2.17E-05 0.002 3.777 1.962 1.814 3.517

Abbreviations: FDR, false discovery rate

Supplementary Notes

List of references for Figure 4 1. PPARA target genes

Type Regulation References Expression PPARA ---| CPS1 (1) Expression PPARA ---| F3 (2) Expression PPARA ---> APOE (3) Expression PPARA ---> MTP (4) Expression PPARA ---> PLIN (5) Expression PPARA ---> SLC2A2 (6) Expression PPARA ---> CYP27A1 (7) Expression PPARA ---> CYP4F3 (8) Expression PPARA ---> PDK4 (9, 10) Expression PPARA ---> POR (11) Expression PPARA ---> SLC35A2 (6) Molecular Transport PPARA ---> GRIN1 (12) Protein Modification PPARA ---> EGFR (13) Regulation HNF4A ---> PPARA (14) Regulation PPARA ---| APOC3 (15) Regulation PPARA ---| CCL2 (16) Regulation PPARA ---| NR1I3 (17) Regulation PPARA ---> CAT (18) Regulation PPARA ---> HNF4A (19) Regulation PPARA ---> SLC2A4 (20, 21) Regulation PPARA ---> ACAA1 (22) Regulation PPARA ---> ACO1 (23) Regulation PPARA ---> BF (24) Regulation PPARA ---> CD36 (25) Regulation PPARA ---> CDS2 (26) Regulation PPARA ---> CYP4F2 (8) Regulation PPARA ---> MLYCD (27) Regulation PPARA ---> PCK2 (9, 28) Regulation PPARA ---> PEX11A (5) Regulation PPARA ---> RXRA (29, 30)

2. SP1 target genes

Type Regulation References Expression SP1 ---> TNFAIP8 (31) Expression SP1 ---> VIM (32) Expression SP1 ---> DDIT3 (33) Expression SP1 ---> MEIS2 (34) Expression SP1 ---> DNM1 (35) Expression SP1 ---> IER3 (36) Expression SP1 ---> FGFR1 (37) Expression SP1 ---> HK2 (38) Expression SP1 ---> SLC2A3 (39, 40) Expression SP1 ---> TLR2 (41, 42) Expression SP1 ---> PLAUR (43) Expression SP1 ---> ALDOA (44) Expression SP1 ---> GPC4 (45) Promoter Binding SP1 ---> MEF2A (46) Promoter Binding SP1 ---> MCAM (47) Promoter Binding SP1 ---> TOP1 (48) Promoter Binding SP1 ---> PDGFA (49) Promoter Binding SP1 ---> ITGAM (50) Promoter Binding SP1 ---> FBLN1 (51) Promoter Binding SP1 ---> ABCC1 (52) Regulation SP1 ---> COL1A1 (53, 54) Regulation SP1 ---> CTGF (55) Regulation SP1 ---> PC4 (56) Regulation SP1 ---> BCL2 (57) Regulation SP1 ---> PSAP (58)

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