Supplemental Table 1. Results of Gene Set Enrichment Analysis Gene sets enriched in the high-risk tumors EMT_UP RANK IN GENE PROBE LIST RANK METRIC SCORE RES CORE_ENRICHMENT INHBA 0 1.166400194 0.114227 Yes HIF1A 2 0.878980517 0.200158 Yes PROCR 96 0.582403243 0.243309 Yes MMP2 109 0.573185384 0.29765 Yes PDGFRA 139 0.551990926 0.347378 Yes TNC 276 0.476955742 0.373783 Yes IFITM3 357 0.439593673 0.404889 Yes S100A8 394 0.42652753 0.441285 Yes PPIC 407 0.418723643 0.480499 Yes UPP1 412 0.417242318 0.520763 Yes CMKOR1 483 0.38994652 0.548501 Yes CYP1B1 514 0.379166543 0.581154 Yes MMP12 614 0.343893617 0.600051 Yes CXCL1 712 0.314516664 0.616371 Yes SPARC 861 0.280738533 0.621768 Yes SLPI 990 0.254141092 0.627546 Yes PRSS11 1041 0.243665695 0.643944 Yes B2M 1130 0.224224433 0.652764 Yes STAT1 1157 0.218002364 0.670232 Yes DCN 1211 0.208057731 0.682694 Yes PDGFRB 1297 0.194911718 0.689092 Yes PMP22 1347 0.186484873 0.700039 Yes GBP3 1376 0.182663307 0.713747 Yes IRF7 1750 0.129845992 0.670775 No CD68 1898 0.111322127 0.65973 No COL6A2 2270 0.070451744 0.61124 No DAB2 2960 -0.005382785 0.5089 No PCOLCE 3441 -0.056272008 0.442748 No FMO1 3562 -0.068788476 0.431569 No BCL3 4014 -0.113547899 0.375355 No MTHFD2 5812 -0.303183019 0.136757 No NF-kB_INDUCED RANK IN GENE PROBE LIST RANK METRIC SCORE RES CORE_ENRICHMENT IL8 8 0.776689529 0.052869 Yes SERPINE1 38 0.645707786 0.093474 Yes KRT14 98 0.580734432 0.125063 Yes BCL2A1 127 0.558770061 0.159766 Yes MMP1 137 0.552590787 0.196885 Yes NFKB2 239 0.49288556 0.216068 Yes TNC 276 0.476955742 0.243877 Yes TNIP1 476 0.391241789 0.241304 Yes CXCL6 526 0.373474061 0.259963 Yes SPRR1B 541 0.36730957 0.283435 Yes KRT10 606 0.34649682 0.297969 Yes

1 SEC24A 625 0.340020001 0.318943 Yes IL1RN 628 0.338782549 0.342227 Yes IER3 673 0.325819731 0.358317 Yes CXCL1 712 0.314516664 0.374519 Yes PLAU 730 0.308055073 0.393417 Yes SOD2 777 0.300054312 0.407414 Yes GADD45A 788 0.296617687 0.426565 Yes ETS1 918 0.269503981 0.426003 Yes MMP14 984 0.255517632 0.434053 Yes ARHE 994 0.252833337 0.450306 Yes IL1B 1071 0.238035232 0.455492 Yes WNT5A 1222 0.206905574 0.447427 No IL7R 1274 0.198788449 0.453625 No CD9 1384 0.181041569 0.449901 No CDKN1A 1609 0.147626579 0.426625 No GBP1 1614 0.147168472 0.43627 No BMP2 2150 0.083626799 0.361954 No MAP2K3 2220 0.075453065 0.356871 No GABBR1 2416 0.052392308 0.331309 No IL6 2500 0.042144474 0.32181 No SPTBN1 2828 0.009254086 0.273473 No RAC2 2920 -8.11E-04 0.259898 No RELA 3174 -0.029199556 0.224034 No EFNA1 3267 -0.038833011 0.212957 No CFLAR 3349 -0.047014389 0.204096 No TAP1 3627 -0.075270794 0.167844 No RAC1 3943 -0.106225885 0.128055 No TAF15 3969 -0.108846299 0.131887 No CD83 3973 -0.109206475 0.13904 No ARHGDIB 4139 -0.124599971 0.122998 No CCNB1 4475 -0.15515919 0.08362 No IFNAR2 4956 -0.205050692 0.025994 No PLAT 5368 -0.252064586 -0.01802 No CPNE5 5698 -0.289424479 -0.04716 No TNFAIP2 5778 -0.297972918 -0.03825 No NPR1 5831 -0.30567655 -0.02476 No MYBL1 5965 -0.326094478 -0.02198 No KRT7 6049 -0.338547945 -0.01084 No TIAM1 6073 -0.342583179 0.009559 No AP2B1 6132 -0.354170918 0.025525 No LITAF 6274 -0.385660231 0.031252 No FGF5 6614 -0.525813758 0.017076 No CR_CAM RANK IN GENE PROBE LIST RANK METRIC SCORE RES CORE_ENRICHMENT GJB2 1 0.931775153 0.134617 Yes IL8 8 0.776689529 0.246057 Yes JUP 26 0.671076417 0.340578 Yes MMP1 137 0.552590787 0.404069 Yes TNC 276 0.476955742 0.452438 Yes PKP1 907 0.271678239 0.397618 Yes

2 CD44 1062 0.239677474 0.409278 Yes CD47 1063 0.239460543 0.443912 Yes CDH1 1179 0.213261619 0.457577 Yes SDC1 1424 0.175255567 0.446475 Yes TIMP2 1554 0.155880406 0.449749 Yes SERPINB5 1586 0.151062399 0.466967 Yes PECAM1 1779 0.12596558 0.456504 No ITGA4 2007 0.098863773 0.436892 No TIMP3 2163 0.081898823 0.425582 No CXCR3 2219 0.075484432 0.428284 No CD99 2327 0.063581012 0.421495 No PCDH1 2468 0.046307918 0.407279 No ITGB5 2486 0.044268209 0.411142 No CD58 2488 0.043679893 0.41731 No ITGAL 2507 0.041701451 0.420652 No PTK2 2743 0.017821951 0.388124 No FAT 2871 0.004597681 0.369817 No ITGAE 2975 -0.007022976 0.355446 No DSC3 2997 -0.008659075 0.353561 No SELPLG 3194 -0.031485934 0.328835 No ITGB4 3345 -0.046355106 0.313131 No CEACAM1 3472 -0.059424289 0.302903 No ADD3 3574 -0.06978482 0.297908 No ARHGAP1 3726 -0.08436159 0.287553 No RAC1 3943 -0.106225885 0.270649 No ALCAM 5201 -0.231638402 0.116372 No VCAM1 5347 -0.248981103 0.130722 No SEMA4D 5430 -0.258362174 0.15584 No F2R 5469 -0.262149125 0.188079 No cell_adhesion RANK IN GENE PROBE LIST RANK METRIC SCORE RES CORE_ENRICHMENT IL8 8 0.776689529 0.07612 Yes JUP 26 0.671076417 0.140379 Yes TGFBI 43 0.64209789 0.201903 Yes ATP2A2 172 0.529284179 0.235436 Yes LOXL2 238 0.492982566 0.274783 Yes TNC 276 0.476955742 0.316725 Yes CSPG2 515 0.378353834 0.318771 Yes TGFB1I1 562 0.360350132 0.347758 Yes PTPNS1 585 0.353595793 0.379665 Yes CCR1 629 0.338624686 0.406939 Yes CD151 708 0.315836966 0.426706 Yes ISLR 832 0.289862245 0.437154 Yes AEBP1 856 0.281377912 0.461722 Yes ARHE 994 0.252833337 0.466388 Yes BAIAP1 1941 0.106707044 0.335436 No NEDD9 1998 0.100221395 0.337032 No ITGA4 2007 0.098863773 0.345676 No CCL4 2091 0.089794785 0.342193 No CXCR3 2219 0.075484432 0.330701 No

3 DSC2 2234 0.074126191 0.335985 No ENTPD1 2337 0.061905392 0.326883 No VWF 2471 0.045918733 0.31155 No CD58 2488 0.043679893 0.313503 No ITGAL 2507 0.041701451 0.314961 No CD164 2763 0.015326634 0.278324 No NINJ1 2862 0.005447823 0.2642 No FAT 2871 0.004597681 0.263461 No DDR1 2952 -0.004752771 0.251961 No DSC3 2997 -0.008659075 0.246238 No SELPLG 3194 -0.031485934 0.22004 No ITGB4 3345 -0.046355106 0.202206 No CIB1 3469 -0.059108116 0.189683 No CLDN1 3539 -0.066096842 0.185936 No SPG7 3591 -0.071653374 0.185437 No FLJ10539 3625 -0.074962005 0.18796 No RAC1 3943 -0.106225885 0.151094 No CX3CL1 4143 -0.124958858 0.133751 No SERF2 4383 -0.147132769 0.11263 No TSC1 4556 -0.164063394 0.103221 No GPR56 4977 -0.207721218 0.061044 No ITGB3BP 5047 -0.215150014 0.072135 No ALCAM 5201 -0.231638402 0.072297 No SEMA4D 5430 -0.258362174 0.063894 No PPFIBP1 5656 -0.283255726 0.058419 No CELSR1 5664 -0.284025609 0.085645 No ARVCF 6108 -0.348646343 0.054054 No PTPRF 6282 -0.38758406 0.066747 No

Gene sets enriched in the low-risk tumors mRNA_splicing PROBE RANK IN GENE LIST RANK METRIC SCORE RES CORE_ENRICHMENT IVNS1ABP 373 0.434517056 1.69E-05 No SMNDC1 901 0.272630453 -0.04374 No SF3B4 1314 0.19196558 -0.08067 No SNRPG 2769 0.014857733 -0.29601 No KHSRP 2775 0.014022015 -0.29496 No PRPF4 2941 -0.003800827 -0.31912 No PPAN 2963 -0.00560919 -0.32154 No SFRS2IP 2971 -0.006775739 -0.32172 No SFRS11 3099 -0.021313885 -0.33796 No NCBP1 3306 -0.04277651 -0.36325 No SFPQ 3567 -0.0691825 -0.39322 No SNRPA1 3809 -0.093889244 -0.41718 No SFRS10 3958 -0.107787833 -0.42546 No SF3A2 4594 -0.167847216 -0.49881 Yes SNRP70 4615 -0.169623882 -0.48003 Yes SF3B3 4624 -0.170936838 -0.4593 Yes NOL3 4737 -0.182281986 -0.45264 Yes SNRPC 4815 -0.190213189 -0.43974 Yes

4 SF3A1 4914 -0.20031786 -0.42869 Yes FNBP3 4938 -0.203017861 -0.40608 Yes HNRPC 5260 -0.238569707 -0.42343 Yes USP39 5283 -0.240810066 -0.39582 Yes PTBP1 5386 -0.254033387 -0.37847 Yes DDX23 5409 -0.256111413 -0.3489 Yes U5-116KD 5416 -0.256759703 -0.31685 Yes SNRPD2 5556 -0.271107912 -0.30284 Yes SNRPD1 5601 -0.276094615 -0.27399 Yes SFRS7 5798 -0.300576866 -0.26471 Yes NONO 5887 -0.31485936 -0.23747 Yes SF3A3 5901 -0.31625843 -0.19883 Yes SNRPB 5932 -0.321726769 -0.16204 Yes LSM1 6208 -0.371609598 -0.15545 Yes U2AF1 6350 -0.407439351 -0.12425 Yes U2AF1L2 6408 -0.423343331 -0.07845 Yes SNRPB2 6543 -0.473365813 -0.03774 Yes PRPF18 6598 -0.508441567 0.019423 Yes CR_CELL_CYCLE PROBE RANK IN GENE LIST RANK METRIC SCORE RES CORE_ENRICHMENT CDK6 597 0.350301504 -0.05068 No GADD45B 608 0.345359713 -0.01419 No MAD1L1 747 0.30484435 -0.00128 No RB1 913 0.270847857 0.003859 No CCND2 1212 0.208016932 -0.01779 No CCND1 1471 0.167422533 -0.03793 No CDKN1A 1609 0.147626579 -0.04216 No CDC2L5 1900 0.111012921 -0.07329 No MAX 2134 0.085515447 -0.0987 No CDC42 2826 0.009316019 -0.20093 No CDC27 2904 6.25E-04 -0.21237 No SKP2 3263 -0.038583521 -0.26162 No BTG2 3298 -0.041858386 -0.2621 No CDC20 3499 -0.062056169 -0.28516 No CDC16 3513 -0.063029513 -0.28017 No NPM1 3612 -0.073597796 -0.28672 No CDC25B 3615 -0.074415356 -0.27883 No CCNH 3733 -0.085116111 -0.28695 No CHES1 3801 -0.093062706 -0.28673 No MAD 4073 -0.118599862 -0.31418 No GSPT1 4097 -0.120867796 -0.30432 No CCNB1 4475 -0.15515919 -0.34359 No SKP1A 4797 -0.188712105 -0.3708 No CDKN1B 5184 -0.229772076 -0.40321 No ERH 5321 -0.245564312 -0.39652 No CKS2 5605 -0.276546627 -0.40839 No RBL1 5705 -0.290500611 -0.39123 No TP53 6129 -0.353418976 -0.41557 Yes HUS1 6204 -0.370534807 -0.38587 Yes CCND3 6281 -0.387386441 -0.35461 Yes

5 E2F1 6466 -0.442169279 -0.33347 Yes MAD2L1 6471 -0.443606436 -0.28528 Yes CDC2 6627 -0.535366535 -0.24955 Yes CDK2 6661 -0.574376404 -0.1913 Yes CDC7 6663 -0.576771319 -0.12801 Yes CENPF 6693 -0.619865537 -0.06416 Yes BUB3 6702 -0.629522324 0.003885 Yes mRNA_processing PROBE RANK IN GENE LIST RANK METRIC SCORE RES CORE_ENRICHMENT SMNDC1 901 0.272630453 -0.10289 No SF3B4 1314 0.19196558 -0.1421 No LSM5 1325 0.190240353 -0.12146 No SLU7 1553 0.156012878 -0.13721 No KHSRP 2775 0.014022015 -0.31801 No SFRS2IP 2971 -0.006775739 -0.34636 No SFRS11 3099 -0.021313885 -0.36285 No DHX15 3398 -0.051323235 -0.4014 No HNRPR 3460 -0.05850073 -0.40371 No SFPQ 3567 -0.0691825 -0.41149 No SFRS10 3958 -0.107787833 -0.45722 No SLBP 4503 -0.158474132 -0.52005 No SNRP70 4615 -0.169623882 -0.5169 No SF3B3 4624 -0.170936838 -0.4982 No SF3A1 4914 -0.20031786 -0.51806 Yes SFRS9 5026 -0.212688893 -0.50989 Yes SFRS1 5050 -0.21552074 -0.48825 Yes CUGBP1 5094 -0.220193028 -0.46904 Yes U2AF2 5197 -0.231281951 -0.45737 Yes USP39 5283 -0.240810066 -0.44204 Yes PTBP1 5386 -0.254033387 -0.42771 Yes U5-116KD 5416 -0.256759703 -0.40216 Yes LSM3 5578 -0.273623258 -0.39437 Yes SFRS7 5798 -0.300576866 -0.39211 Yes HNRPA0 5843 -0.307566881 -0.36289 Yes NONO 5887 -0.31485936 -0.33267 Yes SF3A3 5901 -0.31625843 -0.2978 Yes KHDRBS1 5982 -0.328814119 -0.27148 Yes HNRPA1 6031 -0.335646391 -0.23959 Yes LSM1 6208 -0.371609598 -0.22264 Yes SFRS5 6267 -0.383363813 -0.18669 Yes CPSF6 6278 -0.386668801 -0.14318 Yes U2AF1 6350 -0.407439351 -0.10636 Yes FUSIP1 6375 -0.413496345 -0.06183 Yes SNRPB2 6543 -0.473365813 -0.03168 Yes PRPF18 6598 -0.508441567 0.019423 Yes Cell_Cycle PROBE RANK IN GENE LIST RANK METRIC SCORE RES CORE_ENRICHMENT HDAC4 219 0.504046619 0.006334 No CDK6 597 0.350301504 -0.02288 No MAD1L1 747 0.30484435 -0.02152 No

6 ATM 762 0.301861435 -2.09E-04 No GADD45A 788 0.296617687 0.01905 No RB1 913 0.270847857 0.021509 No CCND2 1212 0.208016932 -0.00692 No CDKN1A 1609 0.147626579 -0.05469 No E2F3 1787 0.125444904 -0.07142 No HDAC3 2174 0.080297247 -0.12291 No SKP2 3263 -0.038583521 -0.2826 No E2F4 3363 -0.048342694 -0.29366 No CDC20 3499 -0.062056169 -0.30903 No CDC25B 3615 -0.074415356 -0.32046 No CCNH 3733 -0.085116111 -0.33135 No YWHAG 4025 -0.11468859 -0.36597 No SMC1L1 4341 -0.142640829 -0.40201 No CCNB1 4475 -0.15515919 -0.40987 No CDKN1B 5184 -0.229772076 -0.49791 No ORC6L 5217 -0.234199017 -0.48454 No PKMYT1 5468 -0.262003571 -0.50161 No CCNB2 5512 -0.266238958 -0.48739 No PRKDC 5695 -0.28914234 -0.49219 No PTTG1 5922 -0.320034057 -0.50117 Yes HDAC5 5946 -0.323516786 -0.47952 Yes MCM7 6012 -0.333072901 -0.46342 Yes PTTG3 6040 -0.336923957 -0.44133 Yes TP53 6129 -0.353418976 -0.42709 Yes CCND3 6281 -0.387386441 -0.41963 Yes MCM4 6392 -0.417973548 -0.40368 Yes HDAC2 6460 -0.439773351 -0.3796 Yes E2F1 6466 -0.442169279 -0.34606 Yes MAD2L1 6471 -0.443606436 -0.31227 Yes MCM3 6573 -0.491765529 -0.28924 Yes CDC2 6627 -0.535366535 -0.25566 Yes HDAC7A 6634 -0.541365087 -0.21458 Yes MCM2 6650 -0.561752856 -0.17327 Yes CDK2 6661 -0.574376404 -0.13023 Yes CDC7 6663 -0.576771319 -0.08567 Yes MCM6 6676 -0.596889973 -0.04118 Yes BUB3 6702 -0.629522324 0.003888 Yes

7