Supplementary Materials:

“Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer”

Viswam S. Nair,1 Olivier Gevaert,4 Guido Davidzon,3 Sandy Napel,4 Edward E. Graves,5 Chuong D. Hoang,2,6 Joseph B. Shrager 2,6 Andrew Quon,3 Daniel L. Rubin,4 & Sylvia K. Plevritis4

Divisions of Pulmonary & Critical Care Medicine,1 Thoracic Surgery,2 Nuclear Medicine3 and the Departments of Radiology4 and Radiation Oncology,5 Stanford University School of Medicine; Veterans Administration Palo Alto Healthcare System6

Supplement 1: External data set cohort characteristics Supplement 2: Study cohort metagenes significantly associated with FDG uptake features Supplement 3: DAVID and GSEA enrichment analysis for metagenes in study cohort Supplement 4: Predicted FDG uptake features enrichment analysis Supplement 5: Kaplan Meier curves for single associated with FDG uptake features and survival Supplement 6: Survival analysis incorporating imaging features with known variables of prognosis in non-small cell lung cancer Supplement 7: IPA networks for SUVmax and the compound model Supplement 8: SUVmax associations with selected glycolytic genes by SAM

! Supplement 1: External data set cohort characteristics !

Variable n (IQR or %) Age (years) 60 (53–67) Tumor Size (cm) 3.5 (2.7–4.5) Gender Female 30 (48) Male 33 (52) Stage I 39 (62) II 12 (19) III 12 (19) Histology Adenocarcinoma 63 (100) Smoking Status No 35 (56) Yes 28 (44) Differentiation Well 14 (22) Moderate 23 (37) Poor 21 (33) Unknown 5 (8) Adjuvant Radiation Therapy No 41 (65) Yes 22 (35) Adjuvant Chemotherapy No 54 (86) Yes 9 (14) Vital Status Alive 39 (62) Expired 24 (38) Time to Vital Status (months) 42 (24–49) IQR = Interquartile Range Supplement 2: Study cohort metagenes significantly associated with FDG uptake features

Metagene GeneID GeneDescription 10 PFKFB3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 10 ACTA2 actin, alpha 2, smooth muscle, aorta 10 ANGPTL2 angiopoietin-like 2 10 ANTXR1 anthrax toxin receptor 1 10 CDH11 cadherin 11, type 2, OB-cadherin (osteoblast) 10 CDH2 cadherin 2, type 1, N-cadherin (neuronal) 10 CTSK cathepsin K 10 COL1A1 collagen, type I, alpha 1 10 COL1A2 collagen, type I, alpha 2 10 COL3A1 collagen, type III, alpha 1 10 CYGB cytoglobin 10 DACT3 dapper, antagonist of beta-catenin, homolog 3 (Xenopus laevis) 10 DCN decorin 10 EFEMP2 EGF-containing fibulin-like extracellular matrix 2 10 EMILIN1 elastin microfibril interfacer 1 10 FBLN1 fibulin 1 10 FLNC filamin C, gamma 10 FSTL1 follistatin-like 1 10 GAS1 growth arrest-specific 1 10 HOXA5 homeobox A5 10 HTRA1 HtrA serine peptidase 1 10 JAM3 junctional adhesion molecule 3 10 MAN1A1 mannosidase, alpha, class 1A, member 1 10 MAPRE2 microtubule-associated protein, RP/EB family, member 2 10 NKD2 naked cuticle homolog 2 (Drosophila) 10 NBL1 neuroblastoma, suppression of tumorigenicity 1 10 OLFML2B olfactomedin-like 2B 10 POSTN periostin, osteoblast specific factor 10 PDGFRA platelet-derived growth factor receptor, alpha polypeptide 10 PODN podocan 10 PTRF polymerase I and transcript release factor 10 RGS2 regulator of G-protein signaling 2, 24kDa 10 RARRES2 retinoic acid receptor responder (tazarotene induced) 2 10 SFRP2 secreted frizzled-related protein 2 10 SPARC secreted protein, acidic, cysteine-rich () 10 SCG5 secretogranin V (7B2 protein) 10 SPON1 spondin 1, extracellular matrix protein 10 SOX8 SRY (sex determining region Y)-box 8 10 SULF1 sulfatase 1 10 SYTL2 synaptotagmin-like 2 10 TSHZ3 teashirt zinc finger homeobox 3 10 THBS1 thrombospondin 1 10 TAGLN transgelin 10 VCAN versican 10 ZNF521 zinc finger protein 521 10 SEPT11 10 AGTRL1 10 C10ORF10 10 C10ORF56 10 C20ORF100 10 HNT 18 AKAP13 A kinase (PRKA) anchor protein 13 18 AHCYL2 adenosylhomocysteinase-like 2 18 ALDH3A2 aldehyde dehydrogenase 3 family, member A2 18 AGA aspartylglucosaminidase 18 ATOH8 atonal homolog 8 (Drosophila) 18 CACNA2D2 calcium channel, voltage-dependent, alpha 2/delta subunit 2 18 F3 coagulation factor III (thromboplastin, tissue factor) 18 C5 complement component 5 18 CKB creatine kinase, brain 18 CCND3 cyclin D3 18 CRELD2 cysteine-rich with EGF-like domains 2 18 FCHO2 FCH domain only 2 18 GPX3 glutathione peroxidase 3 (plasma) 18 KBTBD11 kelch repeat and BTB (POZ) domain containing 11 18 MSLN mesothelin 18 MOSC1 MOCO sulphurase C-terminal domain containing 1 18 MAOA monoamine oxidase A 18 NEDD4L neural precursor cell expressed, developmentally down-regulated 4-like 18 NEDD9 neural precursor cell expressed, developmentally down-regulated 9 18 ODC1 ornithine decarboxylase 1 18 PLA2G10 phospholipase A2, group X 18 KCNK1 potassium channel, subfamily K, member 1 18 PGC progastricsin (pepsinogen C) 18 RASD1 RAS, dexamethasone-induced 1 18 RHOBTB2 Rho-related BTB domain containing 2 18 SCNN1B sodium channel, nonvoltage-gated 1, beta 18 SLC27A3 solute carrier family 27 (fatty acid transporter), member 3 18 SFTPB surfactant protein B 18 TXNDC11 thioredoxin domain containing 11 18 TMEM87A transmembrane protein 87A 18 WWC3 WWC family member 3 18 ZBTB20 zinc finger and BTB domain containing 20 18 EVI1 18 KIAA0256 18 HS.568928 18 LOC400451 18 SNF1LK 18 HS.556018 26 ASCL2 achaete-scute complex homolog 2 (Drosophila) 26 CDC42EP4 CDC42 effector protein (Rho GTPase binding) 4 26 GLCE glucuronic acid epimerase 26 HMMR hyaluronan-mediated motility receptor (RHAMM) 26 IRF9 interferon regulatory factor 9 26 ISG15 ISG15 ubiquitin-like modifier 26 MAD2L2 MAD2 mitotic arrest deficient-like 2 (yeast) 26 MCM3 minichromosome maintenance complex component 3 26 MAP2K2 mitogen-activated protein kinase kinase 2 26 PRELID1 PRELI domain containing 1 26 RFC5 replication factor C (activator 1) 5, 36.5kDa 26 TOP2A topoisomerase (DNA) II alpha 170kDa 26 TPI1 triosephosphate isomerase 1 26 WARS tryptophanyl-tRNA synthetase 26 TNFRSF21 tumor necrosis factor receptor superfamily, member 21 26 C16ORF33 26 FLJ43692 26 LOC732165 30 CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 30 DUSP5 dual specificity phosphatase 5 30 FAM46C family with sequence similarity 46, member C 30 IGJ immunoglobulin J polypeptide, linker protein for immunoglobulin alpha and mu polypeptides 30 JSRP1 junctional sarcoplasmic reticulum protein 1 30 MMP7 matrix metallopeptidase 7 (matrilysin, uterine) 30 MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) 30 MXRA5 matrix-remodelling associated 5 30 MT1E metallothionein 1E 30 PIM2 pim-2 oncogene 30 RGS1 regulator of G-protein signaling 1 30 SEC22B SEC22 vesicle trafficking protein homolog B (S. cerevisiae) (gene/pseudogene) 30 STAMBPL1 STAM binding protein-like 1 30 UBE2J1 ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog, yeast) 30 HS.407903 30 LOC642113 30 LOC647450 30 LOC649923 30 LOC652493 30 LOC652694 30 MGC29506 30 MMP1 70 ATP2A2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 70 ATP6V0E2 ATPase, H+ transporting V0 subunit e2 70 BCAP31 B-cell receptor-associated protein 31 70 CALR 70 CHD4 chromodomain helicase DNA binding protein 4 70 CST1 cystatin SN 70 DIAPH1 diaphanous homolog 1 (Drosophila) 70 DGCR2 DiGeorge syndrome critical region gene 2 70 ENO1 enolase 1, (alpha) 70 EXTL3 exostoses (multiple)-like 3 70 HIGD2A HIG1 hypoxia inducible domain family, member 2A 70 ITFG3 integrin alpha FG-GAP repeat containing 3 70 KPNA6 karyopherin alpha 6 (importin alpha 7) 70 LGALS3BP lectin, galactoside-binding, soluble, 3 binding protein 70 LASP1 LIM and SH3 protein 1 70 MKLN1 muskelin 1, intracellular mediator containing kelch motifs 70 MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse) 70 NUCB1 nucleobindin 1 70 POGK pogo transposable element with KRAB domain 70 ARHGDIA Rho GDP dissociation inhibitor (GDI) alpha 70 ARHGAP1 Rho GTPase activating protein 1 70 RHBDD2 rhomboid domain containing 2 70 SERINC2 serine incorporator 2 70 STIP1 stress-induced-phosphoprotein 1 70 TAPBP TAP binding protein (tapasin) 70 TOMM70A translocase of outer mitochondrial membrane 70 homolog A (S. cerevisiae) 70 TMED9 transmembrane emp24 protein transport domain containing 9 70 TNFRSF1A tumor necrosis factor receptor superfamily, member 1A 70 UCP2 uncoupling protein 2 (mitochondrial, proton carrier) 70 WBP2 WW domain binding protein 2 70 ZDHHC12 zinc finger, DHHC-type containing 12 70 KIAA0152 70 TEGT 70 HS.562504 78 CLDN23 claudin 23 78 COPA coatomer protein complex, subunit alpha 78 COPG2 coatomer protein complex, subunit gamma 2 78 CNIH4 cornichon homolog 4 (Drosophila) 78 ECHS1 enoyl CoA hydratase, short chain, 1, mitochondrial 78 IFI6 interferon, alpha-inducible protein 6 78 LASS2 LAG1 homolog, ceramide synthase 2 78 MFSD3 major facilitator superfamily domain containing 3 78 MFSD5 major facilitator superfamily domain containing 5 78 PNKD paroxysmal nonkinesigenic dyskinesia 78 PAFAH2 platelet-activating factor acetylhydrolase 2, 40kDa 78 RAG1AP1 recombination activating gene 1 activating protein 1 78 SEPX1 selenoprotein X, 1 78 SLC39A1 solute carrier family 39 (zinc transporter), member 1 78 SPSB2 splA/ domain and SOCS box containing 2 78 SDF4 stromal cell derived factor 4 78 TSPAN15 tetraspanin 15 78 TMCO1 transmembrane and coiled-coil domains 1 78 TNFRSF12A tumor necrosis factor receptor superfamily, member 12A 78 ABHD9 86 ALDH1A3 aldehyde dehydrogenase 1 family, member A3 86 ANKDD1A ankyrin repeat and death domain containing 1A 86 CALD1 caldesmon 1 86 CTHRC1 collagen triple helix repeat containing 1 86 DPYSL3 dihydropyrimidinase-like 3 86 FAP fibroblast activation protein, alpha 86 HOXB5 homeobox B5 86 HOXB7 homeobox B7 86 IL32 interleukin 32 86 KIAA1199 KIAA1199 86 LAMB1 laminin, beta 1 86 LEPREL2 leprecan-like 2 86 LRRC15 leucine rich repeat containing 15 86 MT1F metallothionein 1F 86 MT2A metallothionein 2A 86 MFGE8 milk fat globule-EGF factor 8 protein 86 MAP3K5 mitogen-activated protein kinase kinase kinase 5 86 NOX4 NADPH oxidase 4 86 NUAK1 NUAK family, SNF1-like kinase, 1 86 ODZ3 odz, odd Oz/ten-m homolog 3 (Drosophila) 86 PRRX2 paired related homeobox 2 86 PALLD palladin, cytoskeletal associated protein 86 PXDN peroxidasin homolog (Drosophila) 86 RHOC ras homolog gene family, member C 86 RCN3 reticulocalbin 3, EF-hand calcium binding domain 86 SPP1 secreted phosphoprotein 1 86 SIPA1L2 signal-induced proliferation-associated 1 like 2 86 TCF4 transcription factor 4 86 TMEM158 transmembrane protein 158 (gene/pseudogene) 86 TPM2 tropomyosin 2 (beta) 86 WNT10A wingless-type MMTV integration site family, member 10A 86 C1ORF181 100 AMDHD2 amidohydrolase domain containing 2 100 ALK anaplastic lymphoma receptor tyrosine kinase 100 ANXA2P1 pseudogene 1 100 ANTXR2 anthrax toxin receptor 2 100 AXL AXL receptor tyrosine kinase 100 CARD9 caspase recruitment domain family, member 9 100 CMTM3 CKLF-like MARVEL transmembrane domain containing 3 100 GLT25D1 glycosyltransferase 25 domain containing 1 100 IER3 immediate early response 3 100 ITGB5 integrin, beta 5 100 NEK6 NIMA (never in mitosis gene a)-related kinase 6 100 PLAU plasminogen activator, urokinase 100 PARP12 poly (ADP-ribose) polymerase family, member 12 100 PRNP prion protein 100 ARHGEF18 Rho/Rac guanine nucleotide exchange factor (GEF) 18 100 SLC45A3 solute carrier family 45, member 3 100 SORL1 sortilin-related receptor, L(DLR class) A repeats-containing 100 SAMD9 sterile alpha motif domain containing 9 100 TGFBI transforming growth factor, beta-induced, 68kDa 100 TMEM51 transmembrane protein 51 100 TTYH3 tweety homolog 3 (Drosophila) 100 TWF2 twinfilin, actin-binding protein, homolog 2 (Drosophila) 100 VPS18 vacuolar protein sorting 18 homolog (S. cerevisiae) 100 AADACL1 100 SPPL2A Supplement 3: A) DAVID and B) GSEA enrichment analysis for metagenes in study cohort

A) DAVID Enrichment Analysis, q<0.05 Metagene 10 Term Count % PValue FDR signal 29 5.7654076 2.55E-11 3.03E-08 signal peptide 29 5.7654076 2.99E-11 3.96E-08 extracellular matrix 11 2.1868787 2.17E-10 2.57E-07 GO:0031012~extracellular matrix 13 2.584493 2.51E-10 2.83E-07 GO:0044421~extracellular region part 18 3.5785288 7.03E-10 7.93E-07 GO:0005578~proteinaceous extracellular matrix 12 2.3856859 1.83E-09 2.06E-06 Secreted 20 3.9761431 3.15E-09 3.72E-06 GO:0005576~extracellular region 23 4.5725646 6.34E-09 7.15E-06 GO:0001501~skeletal system development 10 1.9880716 1.08E-07 1.58E-04 GO:0043062~extracellular structure organization 8 1.5904573 2.02E-07 2.95E-04 GO:0030198~extracellular matrix organization 7 1.3916501 2.88E-07 4.22E-04 disulfide bond 22 4.3737575 5.35E-07 7.11E-04 disulfide bond 22 4.3737575 8.94E-07 0.001058305 GO:0048407~platelet-derived growth factor binding 4 0.7952286 2.92E-06 0.003402785 GO:0005201~extracellular matrix structural constituent 6 1.1928429 3.15E-06 0.003671341 GO:0019838~growth factor binding 6 1.1928429 8.41E-06 0.009812533 glycoprotein 25 4.9701789 1.02E-05 0.012084042 domain:VWFC 4 0.7952286 1.04E-05 0.013776201 glycosylation site:N-linked (GlcNAc...) 24 4.7713718 1.98E-05 0.026253412 trimer 4 0.7952286 3.20E-05 0.037915614 Metagene 30 metal ion-binding site:Zinc 2; in inhibited form 3 2.0689655 3.34E-05 0.037629859 SUV max/mean clusters only extracellular matrix 3.00E-13 signal 2.98E-12 signal peptide 4.71E-12 GO:0044421~extracellular region part 6.12E-10 GO:0005576~extracellular region 7.32E-10 GO:0031012~extracellular matrix 5.66E-09 Secreted 1.09E-08 GO:0005578~proteinaceous extracellular matrix 1.01E-07 disulfide bond 1.35E-05 disulfide bond 4.68E-05 glycosylation site:N-linked (GlcNAc...) 7.66E-05 glycoprotein 1.17E-04 GO:0001501~skeletal system development 1.78E-04 GO:0030198~extracellular matrix organization 4.65E-04 GO:0005615~extracellular space 0.001117492 GO:0043062~extracellular structure organization 0.002460034 domain:VWFC 0.015901492 calcium 0.023794014 B) GSEA Enrichment Analysis q<0.05 MetageneID Collection GeneSetName Pvalue FDR OverlapGenes 10 MSigDB SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP 7.23E-35 1.73E-31 MMP1//MMP7 10 MSigDB ONDER_CDH1_TARGETS_2_UP 1.69E-20 2.02E-17 ARHGDIA//LGALS3BP//WBP2 10 MSigDB PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP 3.92E-20 3.12E-17 KIAA1199//MFGE8 10 MSigDB ZHU_CMV_ALL_DN 1.53E-17 9.15E-15 RAG1AP1//TMCO1 10 MSigDB SWEET_LUNG_CANCER_KRAS_DN 2.29E-17 1.10E-14 KPNA6//SERINC2 10 MSigDB WEST_ADRENOCORTICAL_TUMOR_DN 5.32E-17 2.12E-14 HIGD2A//TMED9 10 MSigDB ZHU_CMV_24_HR_DN 1.23E-16 4.20E-14 MSLN//PLA2G10//TXNDC11 10 MSigDB VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP 7.37E-16 2.21E-13 ALDH3A2//RASD1 10 MSigDB TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP 7.78E-14 2.07E-11 CDH2//MAPRE2 10 MSigDB FARMER_BREAST_CANCER_CLUSTER_5 2.79E-13 6.67E-11 UBE2J1 10 MSigDB TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_UP 3.67E-13 7.93E-11 CYP1B1 10 MSigDB WEST_ADRENOCORTICAL_TUMOR_MARKERS_DN 3.98E-13 7.93E-11 MT1E 10 MSigDB LIU_PROSTATE_CANCER_DN 2.51E-12 4.38E-10 RGS1 10 MSigDB WANG_SMARCE1_TARGETS_UP 2.56E-12 4.38E-10 MMP9 10 MSigDB DANG_REGULATED_BY_MYC_DN 3.35E-12 5.34E-10 DUSP5 10 MSigDB LIEN_BREAST_CARCINOMA_METAPLASTIC 1.12E-11 1.67E-09 PFKFB3 10 MSigDB ONDER_CDH1_SIGNALING_VIA_CTNNB1 4.49E-11 6.32E-09 JAM3 10 MSigDB CROONQUIST_STROMAL_STIMULATION_UP 9.28E-11 1.23E-08 SPON1 10 MSigDB SENGUPTA_NASOPHARYNGEAL_CARCINOMA_UP 2.92E-10 3.67E-08 POSTN 10 MSigDB LINDGREN_BLADDER_CANCER_CLUSTER_2B 3.07E-10 3.67E-08 ZNF521 10 MSigDB KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN 8.12E-10 9.26E-08 COL1A1//PTRF 10 MSigDB CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_DN 1.25E-09 1.31E-07 AGA 10 MSigDB TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_LOBULAR_NORMAL_DN 1.26E-09 1.31E-07 SFTPB 10 MSigDB LANDIS_ERBB2_BREAST_TUMORS_324_DN 1.84E-09 1.84E-07 NEDD9 10 MSigDB RODWELL_AGING_KIDNEY_NO_BLOOD_UP 2.36E-09 2.26E-07 MOSC1 10 MSigDB CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN 2.71E-09 2.49E-07 ODC1 10 MSigDB CROONQUIST_NRAS_VS_STROMAL_STIMULATION_DN 3.07E-09 2.63E-07 ISG15//MAD2L2 10 MSigDB HOSHIDA_LIVER_CANCER_SUBCLASS_S1 3.07E-09 2.63E-07 GLCE 10 MSigDB ROY_WOUND_BLOOD_VESSEL_UP 1.21E-08 9.98E-07 MCM3 10 MSigDB TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_HSC_UP 1.27E-08 1.01E-06 IGJ 10 MSigDB IZADPANAH_STEM_CELL_ADIPOSE_VS_BONE_DN 1.39E-08 1.07E-06 STAMBPL1 10 MSigDB NAKAMURA_CANCER_MICROENVIRONMENT_UP 4.52E-08 3.38E-06 CHD4//TNFRSF1A 10 MSigDB LANDIS_BREAST_CANCER_PROGRESSION_DN 5.27E-08 3.82E-06 TOMM70A 10 MSigDB BERENJENO_TRANSFORMED_BY_RHOA_DN 6.52E-08 4.54E-06 MKLN1 10 MSigDB TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_LOBULAR_NORMAL_UP 6.64E-08 4.54E-06 SEPX1//TNFRSF12A 10 MSigDB RUIZ_TNC_TARGETS_UP 9.66E-08 6.42E-06 LASS2//SDF4 10 MSigDB GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP 1.17E-07 7.39E-06 ECHS1 10 MSigDB YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_16 1.17E-07 7.39E-06 PNKD 10 MSigDB BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN 1.23E-07 7.54E-06 SPP1 10 MSigDB URS_ADIPOCYTE_DIFFERENTIATION_DN 1.39E-07 8.29E-06 CALD1 10 MSigDB REN_ALVEOLAR_RHABDOMYOSARCOMA_DN 1.82E-07 1.06E-05 FAP 10 MSigDB BROWNE_HCMV_INFECTION_18HR_DN 2.75E-07 1.56E-05 HOXB5//HOXB7 10 MSigDB RIGGI_EWING_SARCOMA_PROGENITOR_DN 2.84E-07 1.58E-05 PALLD 10 MSigDB WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN 2.94E-07 1.60E-05 DPYSL3 10 MSigDB CROMER_TUMORIGENESIS_UP 6.12E-07 3.24E-05 NOX4 10 MSigDB RODWELL_AGING_KIDNEY_UP 6.24E-07 3.24E-05 LRRC15 10 MSigDB EBAUER_TARGETS_OF_PAX3_FOXO1_FUSION_UP 6.42E-07 3.27E-05 MT1F 10 MSigDB BLALOCK_ALZHEIMERS_DISEASE_UP 6.99E-07 3.48E-05 WNT10A 10 MSigDB GERY_CEBP_TARGETS 9.87E-07 4.72E-05 PXDN 10 MSigDB SENESE_HDAC2_TARGETS_DN 9.87E-07 4.72E-05 MAP3K5 10 MSigDB VERRECCHIA_EARLY_RESPONSE_TO_TGFB1 1.23E-06 5.75E-05 VPS18 10 MSigDB SENESE_HDAC1_TARGETS_DN 1.48E-06 6.82E-05 ANXA2P1 10 MSigDB SMID_BREAST_CANCER_LUMINAL_B_DN 1.65E-06 7.45E-05 ALK 10 MSigDB KAAB_HEART_ATRIUM_VS_VENTRICLE_UP 1.85E-06 8.19E-05 ACTA2//CDH11//CDH2//COL1A1//COL1A2//COL3A1//DCN//FBLN1//HOXA5//JAM3//POSTN//SCG5//SPARC//TAGLN//VCAN 10 MSigDB DASU_IL6_SIGNALING_SCAR_DN 1.97E-06 8.57E-05 ACTA2//ANTXR1//CDH11//COL1A1//COL1A2//COL3A1//EMILIN1//FSTL1//PDGFRA//PTRF//RARRES2//SPARC//SULF1//TAGLN 10 MSigDB MCBRYAN_PUBERTAL_BREAST_4_5WK_UP 2.03E-06 8.69E-05 CDH11//COL1A2//COL3A1//FBLN1//GAS1//PDGFRA//POSTN//TAGLN//THBS1//VCAN 10 MSigDB MARTORIATI_MDM4_TARGETS_FETAL_LIVER_DN 2.68E-06 0.00010927 ACTA2//ANGPTL2//CDH11//COL1A1//COL1A2//COL3A1//DCN//HOXA5//PDGFRA//POSTN//PTRF//RARRES2//RGS2//SPARC//TAGLN 10 MSigDB LEE_NEURAL_CREST_STEM_CELL_UP 2.68E-06 0.00010927 CDH2//DCN//EFEMP2//EMILIN1//FBLN1//GAS1//HOXA5//JAM3//NBL1//PDGFRA//POSTN//PTRF//RARRES2//SPON1//TAGLN//VCAN 10 MSigDB NING_CHRONIC_OBSTRUCTIVE_PULMONARY_DISEASE_DN 2.69E-06 0.00010927 CDH11//COL1A2//COL3A1//GAS1//PDGFRA//POSTN//TAGLN//THBS1//VCAN 10 MSigDB THUM_MIR21_TARGETS_HEART_DISEASE_UP 2.86E-06 0.00011419 ANTXR1//CDH11//COL1A2//COL3A1//FSTL1//GAS1//SFRP2//SPARC//SULF1//THBS1//VCAN 10 MSigDB NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP 3.06E-06 0.00011997 COL1A1//COL1A2//COL3A1//POSTN//SFRP2//SPARC//SULF1//VCAN 10 MSigDB MOROSETTI_FACIOSCAPULOHUMERAL_MUSCULAR_DISTROPHY_UP 3.99E-06 0.00015303 COL1A1//COL1A2//COL3A1//POSTN//SFRP2//SULF1//VCAN 10 MSigDB CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN 4.03E-06 0.00015303 DCN//FBLN1//GAS1//PDGFRA//RARRES2//SPON1 10 MSigDB SASSON_RESPONSE_TO_FORSKOLIN_DN 4.13E-06 0.00015455 ACTA2//ANGPTL2//COL1A2//EFEMP2//FLNC//NBL1//PODN//PTRF//RARRES2//SPARC//SPON1//TAGLN 10 MSigDB TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP 4.25E-06 0.00015633 ACTA2//ANTXR1//COL1A1//COL3A1//DCN//POSTN//SULF1//TAGLN//VCAN 10 MSigDB SASSON_RESPONSE_TO_GONADOTROPHINS_DN 4.63E-06 0.00016795 CDH2//COL1A1//COL1A2//COL3A1//FSTL1//GAS1//PDGFRA//POSTN//SPARC//THBS1 10 MSigDB SENESE_HDAC3_TARGETS_DN 7.77E-06 0.00027768 ANGPTL2//COL1A1//COL3A1//DACT3//FSTL1//NBL1//POSTN//SPARC//TAGLN 10 MSigDB WANG_HCP_PROSTATE_CANCER 8.21E-06 0.00028721 COL1A1//COL1A2//COL3A1//POSTN//SFRP2//VCAN 10 MSigDB PAL_PRMT5_TARGETS_UP 8.28E-06 0.00028721 ACTA2//ANGPTL2//COL1A1//COL3A1//FSTL1//HTRA1//POSTN 10 MSigDB GRUETZMANN_PANCREATIC_CANCER_UP 1.43E-05 0.00048785 CDH11//COL1A1//COL1A2//COL3A1//PTRF//SPON1//TAGLN 10 MSigDB CAIRO_HEPATOBLASTOMA_CLASSES_DN 1.63E-05 0.0005486 CALD1//CTHRC1//FAP//KIAA1199//NOX4//NUAK1//SPP1 10 MSigDB HATADA_METHYLATED_IN_LUNG_CANCER_UP 1.70E-05 0.00056535 ACTA2//COL3A1//FSTL1//HOXA5//RGS2//SPARC//VCAN 10 MSigDB SENESE_HDAC1_AND_HDAC2_TARGETS_DN 1.83E-05 0.00059753 COL1A1//COL1A2//COL3A1//POSTN 10 MSigDB AMIT_SERUM_RESPONSE_40_MCF10A 1.87E-05 0.00059753 IL32//MT2A//NUAK1//PALLD//PXDN//TCF4//TMEM158//TPM2 10 MSigDB PETRETTO_CARDIAC_HYPERTROPHY 1.87E-05 0.00059753 ANGPTL2//COL1A1//COL3A1//FSTL1//HTRA1 10 MSigDB COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP 2.05E-05 0.00064579 COL1A1//COL1A2//COL3A1//SULF1//VCAN 10 MSigDB WOO_LIVER_CANCER_RECURRENCE_UP 2.09E-05 0.00064978 CDH11//COL1A2//COL3A1//MAN1A1//OLFML2B//PDGFRA 10 MSigDB KAAB_FAILED_HEART_ATRIUM_UP 2.24E-05 0.00068721 COL3A1//DCN//SPARC//THBS1 10 MSigDB CUI_TCF21_TARGETS_UP 2.44E-05 0.00073911 ANGPTL2//COL3A1//EMILIN1//PTRF//THBS1//VCAN 10 MSigDB MARKEY_RB1_CHRONIC_LOF_UP 2.70E-05 0.00080645 COL1A2//COL3A1//POSTN//SPARC 10 MSigDB VERHAAK_AML_WITH_NPM1_MUTATED_DN 3.50E-05 0.0010341 ACTA2//COL1A1//DCN//PTRF//RGS2//TAGLN 10 MSigDB WONG_ENDMETRIUM_CANCER_DN 3.89E-05 0.0011237 ANGPTL2//COL1A2//DCN//EFEMP2//FBLN1//FLNC//GAS1//PFKFB3//PTRF//RARRES2//SPARC//TAGLN//VCAN 10 MSigDB MARTINEZ_RB1_TARGETS_UP 3.90E-05 0.0011237 ACTA2//DCN//POSTN//RGS2//VCAN 10 MSigDB VANHARANTA_UTERINE_FIBROID_UP 4.47E-05 0.0012743 ATP2A2//CALR//CHD4//EXTL3//LASP1//LGALS3BP//TOMM70A//UCP2 10 MSigDB KHETCHOUMIAN_TRIM24_TARGETS_UP 4.79E-05 0.0013317 PDGFRA//SULF1//THBS1 10 MSigDB MARCHINI_TRABECTEDIN_RESISTANCE_DN 4.79E-05 0.0013317 ACTA2//CDH11//GAS1//HTRA1//SPON1//VCAN 10 MSigDB CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN 5.43E-05 0.0014945 COL1A1//COL1A2//POSTN 10 MSigDB MULLIGHAN_MLL_SIGNATURE_2_DN 5.56E-05 0.0015112 CDH11//COL1A2//COL3A1//CYGB//THBS1//VCAN 10 MSigDB SMID_BREAST_CANCER_NORMAL_LIKE_UP 6.50E-05 0.0017472 ARHGAP1//BCAP31//CHD4//DGCR2//EXTL3//LASP1//LGALS3BP//UCP2 10 MSigDB CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_DN 6.62E-05 0.00176 PDGFRA//POSTN//SCG5 10 MSigDB LEE_LIVER_CANCER_MYC_E2F1_UP 7.81E-05 0.0020534 ACTA2//FLNC//MAPRE2//THBS1 10 MSigDB BENPORATH_NANOG_TARGETS 8.32E-05 0.0021638 IL32//PXDN//TCF4//TPM2 10 MSigDB HELLEBREKERS_SILENCED_DURING_TUMOR_ANGIOGENESIS 9.20E-05 0.0023671 CALR//CHD4//EXTL3//KPNA6//LASP1//TOMM70A//UCP2 10 MSigDB YAMASHITA_METHYLATED_IN_PROSTATE_CANCER 9.70E-05 0.0024114 DCN//HTRA1//NBL1//RARRES2//SPON1 10 MSigDB RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_DN 9.71E-05 0.0024114 DUSP5//FAM46C//MT1E//PIM2//UBE2J1 10 MSigDB BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING 9.71E-05 0.0024114 ANGPTL2//COL1A1//COL1A2//PTRF//RARRES2//TAGLN 10 MSigDB SHEPARD_BMYB_MORPHOLINO_DN 9.77E-05 0.0024114 ALDH1A3//DPYSL3//FAP//MAP3K5//MFGE8//SPP1 10 MSigDB SMIRNOV_CIRCULATING_ENDOTHELIOCYTES_IN_CANCER_UP 0.00010265 0.0025064 ACTA2//FSTL1//TAGLN 10 MSigDB CONCANNON_APOPTOSIS_BY_EPOXOMICIN_DN 0.00010772 0.0026038 FAP//ODZ3//SPP1//WNT10A 10 MSigDB MAHAJAN_RESPONSE_TO_IL1A_DN 0.0001129 0.0027017 ALDH1A3//CALD1//FAP//MFGE8//MT1F//MT2A 10 MSigDB VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP 0.00011566 0.0027404 LAMB1//PALLD//PXDN//TCF4 10 MSigDB WILCOX_PRESPONSE_TO_ROGESTERONE_DN 0.00012441 0.0029059 ANKDD1A//CALD1//DPYSL3//LAMB1//PALLD//TPM2 10 MSigDB PEREZ_TP63_TARGETS 0.00012508 0.0029059 FBLN1//PFKFB3//PTRF 10 MSigDB FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_OK_VS_DONOR_UP 0.00014635 0.0033676 MAN1A1//NBL1//PTRF//SPARC//SPON1 10 MSigDB BLUM_RESPONSE_TO_SALIRASIB_DN 0.00015241 0.0034735 EMILIN1//PDGFRA//TSHZ3 10 MSigDB MARTINEZ_TP53_TARGETS_UP 0.00016329 0.0036547 HMMR//MCM3//RFC5//TOP2A//TPI1 10 MSigDB GU_PDEF_TARGETS_UP 0.00016342 0.0036547 ARHGEF18//AXL//CMTM3//ITGB5//TGFBI 10 MSigDB KAYO_CALORIE_RESTRICTION_MUSCLE_UP 0.00017059 0.0037799 CYP1B1//FAM46C//MMP9//RGS1 10 MSigDB MCBRYAN_PUBERTAL_BREAST_6_7WK_DN 0.00017797 0.0039072 DUSP5//PIM2//UBE2J1 10 MSigDB FRIDMAN_SENESCENCE_UP 0.00022655 0.0048842 FAP//PXDN//SPP1 10 MSigDB KIM_MYCN_AMPLIFICATION_TARGETS_DN 0.00022655 0.0048842 COL1A1//COL1A2//SPARC 10 MSigDB BROWNE_HCMV_INFECTION_16HR_DN 0.00026323 0.0056241 CALD1//MAP3K5//MT1F//RHOC//SPP1//TCF4 10 MSigDB SANA_TNF_SIGNALING_DN 0.0002829 0.0059544 CALD1//FAP//NOX4//SPP1//TCF4 10 MSigDB BLALOCK_ALZHEIMERS_DISEASE_INCIPIENT_UP 0.00028473 0.0059544 MT1F//MT2A//RHOC//TMEM158 10 MSigDB KIM_WT1_TARGETS_UP 0.00028615 0.0059544 COL1A1//COL1A2//SPARC 10 MSigDB BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN 0.00028944 0.0059709 FAM46C//IGJ 10 MSigDB NADERI_BREAST_CANCER_PROGNOSIS_DN 0.0003186 0.0065163 MCM3//RFC5//TOP2A 10 MSigDB KOYAMA_SEMA3B_TARGETS_UP 0.00033557 0.0068053 HMMR//MCM3//RFC5//TOP2A 10 MSigDB BERENJENO_TRANSFORMED_BY_RHOA_FOREVER_UP 0.00035789 0.0071369 IRF9//ISG15//TPI1 10 MSigDB VERRECCHIA_RESPONSE_TO_TGFB1_C1 0.00035789 0.0071369 HMMR//TNFRSF21//TOP2A 10 MSigDB BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_UP 0.00039939 0.007834 MCM3//PRELID1//RFC5//TNFRSF21 10 MSigDB VERRECCHIA_RESPONSE_TO_TGFB1_C2 0.00039939 0.007834 CDH2//TAGLN//VCAN 10 MSigDB MCCABE_HOXC6_TARGETS_DN 0.0004431 0.0086207 HMMR//MCM3//TOP2A//TPI1//WARS 10 MSigDB DODD_NASOPHARYNGEAL_CARCINOMA_DN 0.0004724 0.0091165 CDH11//EMILIN1//PDGFRA//VCAN 10 MSigDB MATSUDA_NATURAL_KILLER_DIFFERENTIATION 0.0004937 0.0094515 HMMR//MCM3//TOP2A//WARS 10 MSigDB CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP 0.00050306 0.0095542 MAPRE2//POSTN//VCAN 10 MSigDB TAVAZOIE_METASTASIS 0.0005177 0.0097548 ANGPTL2//PDGFRA//SFRP2//SPARC 10 MSigDB DORSEY_GAB2_TARGETS 0.00053711 0.0099636 ARHGAP1//CHD4//LASP1 10 MSigDB LU_TUMOR_ENDOTHELIAL_MARKERS_UP 0.00053711 0.0099636 COL1A1//COL1A2//THBS1 10 MSigDB MISHRA_CARCINOMA_ASSOCIATED_FIBROBLAST_DN 0.00058738 0.01073 IRF9//ISG15 10 MSigDB PETRETTO_HEART_MASS_QTL_CIS_UP 0.00058738 0.01073 CYP1B1//DUSP5//MMP9//SEC22B 10 MSigDB SUNG_METASTASIS_STROMA_UP 0.00059492 0.010785 IRF9//ISG15 10 MSigDB CERVERA_SDHB_TARGETS_1_UP 0.00064454 0.011597 ARHGAP1//BCAP31//DGCR2//KPNA6//LASP1//TMED9 10 MSigDB ROZANOV_MMP14_TARGETS_UP 0.0006571 0.011727 ACTA2//CDH11//COL1A2//COL3A1//SPARC//VCAN 10 MSigDB RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN 0.00066155 0.011727 COL1A1//MAPRE2//PFKFB3//RGS2//SCG5 10 MSigDB BENPORATH_SUZ12_TARGETS 0.00071516 0.012584 ISG15//MCM3//TOP2A 10 MSigDB KAN_RESPONSE_TO_ARSENIC_TRIOXIDE 0.00078932 0.013787 CYP1B1//DUSP5//MMP9//SEC22B 10 MSigDB BROWNE_HCMV_INFECTION_48HR_DN 0.0007991 0.013857 ASCL2//IRF9//TNFRSF21 10 MSigDB OHM_METHYLATED_IN_ADULT_CANCERS 0.00081003 0.013941 MAD2L2//RFC5//WARS 10 MSigDB ONKEN_UVEAL_MELANOMA_UP 0.00081563 0.013941 ANTXR1//POSTN//ZNF521 10 MSigDB HORIUCHI_WTAP_TARGETS_UP 0.00083979 0.014253 ANGPTL2//DCN//EFEMP2//FLNC//VCAN 10 MSigDB POOLA_INVASIVE_BREAST_CANCER_UP 0.00085087 0.014339 CDH2//FLNC//PDGFRA//THBS1 10 MSigDB DACOSTA_ERCC3_ALLELE_XPCS_VS_TTD_DN 0.00087104 0.014475 ANTXR1//EFEMP2//SPARC//TAGLN//THBS1//VCAN 10 MSigDB GILDEA_METASTASIS 0.00087104 0.014475 BCAP31//CALR//TMED9 10 MSigDB TOOKER_GEMCITABINE_RESISTANCE_DN 0.0008893 0.014576 DCN//FBLN1 10 MSigDB TOOKER_RESPONSE_TO_BEXAROTENE_UP 0.0008893 0.014576 ANTXR1//SPARC//THBS1//TSHZ3 10 MSigDB LU_TUMOR_VASCULATURE_UP 0.00093416 0.015207 SPARC//VCAN 10 MSigDB LIAO_METASTASIS 0.00095341 0.015416 SPP1//TPM2 10 MSigDB ALONSO_METASTASIS_EMT_UP 0.00099938 0.01605 COL1A2//COL3A1 10 MSigDB ZHU_CMV_8_HR_DN 0.0010667 0.017017 FAP//MT2A 10 MSigDB GAUSSMANN_MLL_AF4_FUSION_TARGETS_F_UP 0.0010884 0.017248 DPYSL3//KIAA1199//NOX4//PXDN//RCN3 10 MSigDB MASSARWEH_TAMOXIFEN_RESISTANCE_UP 0.0011099 0.017428 ACTA2//COL1A1//COL1A2//COL3A1//POSTN//SPARC//SULF1//VCAN 10 MSigDB BENPORATH_ES_WITH_H3K27ME3 0.0011178 0.017428 MT1E//RGS1 10 MSigDB BERENJENO_TRANSFORMED_BY_RHOA_FOREVER_DN 0.0011361 0.017428 GAS1//POSTN//SFRP2//SPON1//SYTL2 10 MSigDB FRIDMAN_IMMORTALIZATION_DN 0.0011361 0.017428 FLNC//MAPRE2//POSTN 10 MSigDB WANG_METHYLATED_IN_BREAST_CANCER 0.0011361 0.017428 COL1A1//PDGFRA//RGS2 10 MSigDB IWANAGA_CARCINOGENESIS_BY_KRAS_PTEN_DN 0.0011617 0.017706 SPARC//THBS1 10 MSigDB GENTILE_UV_RESPONSE_CLUSTER_D2 0.0012076 0.01829 CHD4//ENO1//STIP1 10 MSigDB MARTINEZ_RB1_AND_TP53_TARGETS_UP 0.0012944 0.019481 COL1A1//FSTL1//HTRA1 10 MSigDB MARTINEZ_RB1_AND_TP53_TARGETS_DN 0.001315 0.019668 ANGPTL2//EFEMP2//NKD2//TAGLN 10 MSigDB MARTINEZ_TP53_TARGETS_DN 0.0013359 0.019856 ACTA2//COL3A1//CTSK//FBLN1//TAGLN//THBS1 10 MSigDB BAELDE_DIABETIC_NEPHROPATHY_DN 0.0013568 0.020041 CYP1B1//IGJ//MMP7//SEC22B 10 MSigDB LANDIS_ERBB2_BREAST_TUMORS_65_DN 0.0014344 0.021059 LRRC15//MAP3K5//TMEM158 10 MSigDB VANTVEER_BREAST_CANCER_BRCA1_DN 0.0015141 0.022093 MCM3//RFC5//TPI1 10 MSigDB DAUER_STAT3_TARGETS_UP 0.0015958 0.023144 CDH11//MAN1A1//SULF1//VCAN 10 MSigDB BROWNE_HCMV_INFECTION_2HR_UP 0.0016796 0.024067 ISG15//WARS 10 MSigDB TOMLINS_PROSTATE_CANCER_DN 0.0016796 0.024067 HMMR//MAP2K2//MCM3//RFC5//TOP2A 10 MSigDB BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN 0.0017653 0.025145 PTRF//RGS2//VCAN 10 MSigDB GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP 0.0018102 0.025632 COL1A1//COL1A2//FBLN1//HOXA5//VCAN 10 MSigDB BASAKI_YBX1_TARGETS_DN 0.0018829 0.026505 CDH2//SPARC 10 MSigDB LINDGREN_BLADDER_CANCER_HIGH_RECURRENCE 0.0020345 0.028471 IGJ//PIM2//UBE2J1 10 MSigDB DAVICIONI_MOLECULAR_ARMS_VS_ERMS_DN 0.0021137 0.029408 MMP1//MMP9 10 MSigDB SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP 0.0022706 0.031408 DGCR2//LASP1//SERINC2//TMED9//UCP2 10 MSigDB LY_AGING_OLD_DN 0.002421 0.033105 HOXB7//IL32//KIAA1199//LAMB1 10 MSigDB ZHAN_MULTIPLE_MYELOMA_MS_UP 0.002421 0.033105 IL32//MFGE8//NUAK1//PXDN 10 MSigDB KANNAN_TP53_TARGETS_UP 0.0025225 0.034125 ARHGAP1//TNFRSF1A 10 MSigDB VERHAAK_AML_WITH_NPM1_MUTATED_UP 0.0025241 0.034125 GAS1//SULF1 10 MSigDB ZHONG_RESPONSE_TO_AZACITIDINE_AND_TSA_UP 0.0025635 0.034464 IGJ//MMP7//PIM2//UBE2J1 10 MSigDB EBAUER_MYOGENIC_TARGETS_OF_PAX3_FOXO1_FUSION 0.0026259 0.034909 ARHGAP1//LASP1 10 MSigDB KORKOLA_YOLK_SAC_TUMOR 0.0026259 0.034909 IRF9//MAP2K2 10 MSigDB TARTE_PLASMA_CELL_VS_PLASMABLAST_UP 0.002684 0.035486 CALD1//KIAA1199//TPM2 10 MSigDB THUM_SYSTOLIC_HEART_FAILURE_UP 0.0027084 0.035611 HMMR//MCM3//RFC5 10 MSigDB WU_CELL_MIGRATION 0.0027252 0.035636 HMMR//MCM3//RFC5//TOP2A 10 MSigDB TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP 0.0027665 0.03598 MCM3//TOP2A 10 MSigDB RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_UP 0.0029083 0.037619 ACTA2//SYTL2//THBS1 10 MSigDB DELYS_THYROID_CANCER_UP 0.003038 0.039086 PRNP//SORL1//TGFBI 10 MSigDB HUPER_BREAST_BASAL_VS_LUMINAL_UP 0.0030585 0.039139 KIAA1199//NOX4//PXDN//RCN3 10 MSigDB MANALO_HYPOXIA_UP 0.0032461 0.041318 MT1F//MT2A 10 MSigDB STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN 0.0032861 0.041461 EFEMP2//EMILIN1//FBLN1 10 MSigDB TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP 0.0032919 0.041461 NUAK1//PXDN 10 MSigDB DASU_IL6_SIGNALING_UP 0.0034027 0.04241 ITGB5//PLAU//PRNP//SORL1 10 MSigDB HOQUE_METHYLATED_IN_CANCER 0.0034027 0.04241 HMMR//TOP2A//TPI1 10 MSigDB GOZGIT_ESR1_TARGETS_DN 0.0034921 0.043299 CALD1//DPYSL3//TCF4 10 MSigDB MARKEY_RB1_ACUTE_LOF_DN 0.0035752 0.0441 GLCE//HMMR//RFC5//TOP2A 10 MSigDB AMIT_EGF_RESPONSE_240_HELA 0.0037635 0.045486 MXRA5//RGS1 10 MSigDB CORRE_MULTIPLE_MYELOMA_DN 0.0037635 0.045486 MFGE8//SPP1 10 MSigDB LEE_LIVER_CANCER_DENA_UP 0.0037635 0.045486 MT1F//MT2A 10 MSigDB WAMUNYOKOLI_OVARIAN_CANCER_GRADES_1_2_DN 0.0037635 0.045486 HMMR//MAD2L2//MCM3 10 MSigDB LEE_LIVER_CANCER_E2F1_UP 0.0038875 0.046747 ACTA2//VCAN 10 MSigDB BENPORATH_SOX2_TARGETS 0.003923 0.046939 HOXA5//THBS1//VCAN 10 MSigDB MILI_PSEUDOPODIA_CHEMOTAXIS_DN 0.0039591 0.047077 COL1A2//FLNC//PTRF 10 MSigDB MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP 0.0040132 0.047077 IGJ//UBE2J1 10 MSigDB TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_LOBULAR_NORMAL_DN 0.0040132 0.047077 IGJ//MMP7//RGS1 10 MSigDB URS_ADIPOCYTE_DIFFERENTIATION_UP 0.0040132 0.047077 AXL//TGFBI 10 MSigDB DELYS_THYROID_CANCER_DN 0.0040781 0.047605 ACTA2//TAGLN 10 MSigDB HADDAD_T_LYMPHOCYTE_AND_NK_PROGENITOR_DN 0.0041408 0.048101 CDH2//DCN 10 MSigDB RAMASWAMY_METASTASIS_UP 0.0042701 0.049127 NUAK1//SPP1 10 MSigDB VANHARANTA_UTERINE_FIBROID_DN 0.0042701 0.049127 ANXA2P1//IER3//ITGB5//PLAU 18 MSigDB SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4 5.03E-08 0.00012029 CALD1//DPYSL3//FAP//KIAA1199//LAMB1//LRRC15//NOX4//NUAK1//PALLD//TCF4//TMEM158 18 MSigDB RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN 1.01E-05 0.012028 CTHRC1//LAMB1//LRRC15 18 MSigDB DODD_NASOPHARYNGEAL_CARCINOMA_UP 1.94E-05 0.015487 CDH11//HTRA1 18 MSigDB BLALOCK_ALZHEIMERS_DISEASE_UP 3.67E-05 0.021979 CALD1//PRRX2//TCF4//TMEM158 18 MSigDB NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_DN 8.28E-05 0.039621 COL1A2//SPARC 18 MSigDB ONDER_CDH1_TARGETS_2_DN 0.00011197 0.044659 CDH11//POSTN 26 MSigDB BLUM_RESPONSE_TO_SALIRASIB_DN 4.72E-07 0.0011294 CDH11//COL1A1//COL3A1//EFEMP2//TAGLN 26 MSigDB VECCHI_GASTRIC_CANCER_EARLY_UP 1.21E-06 0.0014463 COL1A1//COL3A1//GAS1//PDGFRA 26 MSigDB KAUFFMANN_MELANOMA_RELAPSE_UP 3.08E-06 0.0022752 HOXB5//PXDN//TCF4//TMEM158 26 MSigDB KOBAYASHI_EGFR_SIGNALING_24HR_DN 5.69E-06 0.0022752 ANTXR1//COL1A1//COL3A1//FBLN1//PTRF//SPARC//TAGLN 26 MSigDB SCIBETTA_KDM5B_TARGETS_DN 7.34E-06 0.0022752 IGJ//MMP7//MMP9//PIM2 26 MSigDB TOOKER_GEMCITABINE_RESISTANCE_UP 7.34E-06 0.0022752 EFEMP2//FLNC//HTRA1//RGS2 26 MSigDB TOOKER_RESPONSE_TO_BEXAROTENE_DN 7.34E-06 0.0022752 FSTL1//GAS1//POSTN//SFRP2//VCAN 26 MSigDB LEE_EARLY_T_LYMPHOCYTE_UP 8.24E-06 0.0022752 COL1A1//CTSK//NBL1//POSTN//SPARC//VCAN 26 MSigDB CROONQUIST_IL6_DEPRIVATION_DN 8.56E-06 0.0022752 DUSP5//MMP9//MXRA5//RGS1 26 MSigDB BASAKI_YBX1_TARGETS_UP 9.51E-06 0.0022752 ARHGAP1//ATP2A2//BCAP31//DGCR2//LASP1//LGALS3BP//TMED9 26 MSigDB CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN 1.14E-05 0.002474 DCN//RGS2//THBS1 26 MSigDB TARTE_PLASMA_CELL_VS_PLASMABLAST_DN 1.35E-05 0.0026929 COL1A1//COL1A2//POSTN//RGS2 26 MSigDB LE_EGR2_TARGETS_UP 1.67E-05 0.0030099 CALD1//DPYSL3//MAP3K5//MT2A//PALLD 26 MSigDB GRADE_COLON_CANCER_UP 1.77E-05 0.0030099 COL3A1//DCN//VCAN 26 MSigDB TSAI_DNAJB4_TARGETS_UP 1.89E-05 0.0030099 DPYSL3//MT1F//MT2A//TMEM158 Supplement 4: Predicted FDG uptake features gene enrichment analysis (DAVID), q < 0.10 Term Bonferroni FDR DAVID Enrichment Analysis for pSUVmean acetylation 0.0000 0.0000 mitosis 0.0000 0.0000 cell division 0.0000 0.0001 acetylated amino end 0.0000 0.0001 GO:0006955~immune response 0.0003 0.0003 GO:0000279~M phase 0.0006 0.0005 GO:0007067~mitosis 0.0008 0.0007 GO:0000280~nuclear division 0.0008 0.0007 GO:0022403~cell cycle phase 0.0009 0.0009 GO:0000087~M phase of mitotic cell cycle 0.0010 0.0010 GO:0051301~cell division 0.0012 0.0011 GO:0048285~organelle fission 0.0015 0.0013 cell cycle 0.0006 0.0022 GO:0000278~mitotic cell cycle 0.0046 0.0042 phosphoprotein 0.0017 0.0057 cytoskeleton 0.0038 0.0128 GO:0022402~cell cycle process 0.0149 0.0139 GO:0006952~defense response 0.0290 0.0272 GO:0007049~cell cycle 0.0351 0.0330 DAVID Enrichment Analysis for pSUVvariance mitosis 0.0001 0.0003 endoplasmic reticulum 0.0001 0.0004 GO:0000279~M phase 0.0017 0.0018 cell division 0.0006 0.0022 GO:0000280~nuclear division 0.0043 0.0045 GO:0007067~mitosis 0.0043 0.0045 GO:0000087~M phase of mitotic cell cycle 0.0055 0.0058 GO:0048285~organelle fission 0.0074 0.0078 GO:0051301~cell division 0.0161 0.0170 GO:0022403~cell cycle phase 0.0213 0.0227 extracellular matrix 0.0139 0.0477 cell cycle 0.0148 0.0506 GO:0006955~immune response 0.0475 0.0512 centromere 0.0228 0.0784 DAVID Enrichment Analysis for pSUVmin acetylation 0.0000 0.0000 endoplasmic reticulum 0.0001 0.0004 extracellular matrix 0.0003 0.0007 signal 0.0009 0.0025 signal peptide 0.0031 0.0033 GO:0005783~endoplasmic reticulum 0.0104 0.0359 GO:0045121~membrane raft 0.0119 0.0410 GO:0005578~proteinaceous extracellular matrix 0.0159 0.0549 short sequence motif:Cell attachment site 0.0669 0.0732 GO:0031012~extracellular matrix 0.0214 0.0739 DAVID Enrichment Analysis for pSUVpca2 lysosome 0.0000 0.0000 GO:0000323~lytic vacuole 0.0000 0.0000 GO:0005764~lysosome 0.0000 0.0000 hsa04612:Antigen processing and presentation 0.0000 0.0000 GO:0005773~vacuole 0.0000 0.0000 region of interest:Connecting peptide 0.0000 0.0000 GO:0006955~immune response 0.0001 0.0001 region of interest:Alpha-2 0.0002 0.0003 region of interest:Alpha-1 0.0002 0.0003 domain:Ig-like C1-type 0.0002 0.0003 transmembrane protein 0.0001 0.0005 heterodimer 0.0002 0.0006 SM00407:IGc1 0.0001 0.0006 IPR003597:Immunoglobulin C1-set 0.0004 0.0007 hsa05330:Allograft rejection 0.0001 0.0011 signal 0.0003 0.0012 GO:0019882~antigen processing and presentation 0.0015 0.0012 hsa05416:Viral myocarditis 0.0002 0.0016 GO:0002504~antigen processing and presentation of peptide or polysaccharide antigen via MHC class II 0.0019 0.0016 signal peptide 0.0016 0.0019 hsa05332:Graft-versus-host disease 0.0003 0.0023 GO:0042611~MHC protein complex 0.0006 0.0023 hsa04514:Cell adhesion molecules (CAMs) 0.0003 0.0027 immune response 0.0011 0.0037 GO:0005783~endoplasmic reticulum 0.0011 0.0045 hsa04940:Type I diabetes mellitus 0.0006 0.0045 GO:0032395~MHC class II receptor activity 0.0018 0.0046 mhc ii 0.0017 0.0057 IPR003006:Immunoglobulin/major histocompatibility complex, conserved site 0.0047 0.0090 hsa04142:Lysosome 0.0018 0.0141 membrane 0.0047 0.0159 hsa05320:Autoimmune thyroid disease 0.0031 0.0243 endoplasmic reticulum 0.0098 0.0328 GO:0044459~plasma membrane part 0.0107 0.0448 duplication 0.0211 0.0710 GO:0048002~antigen processing and presentation of peptide antigen 0.0917 0.0816 DAVID Enrichment Analysis for Multivariate-pSUV acetylation 0.0000 0.0000 GO:0006955~immune response 0.0000 0.0000 transmembrane protein 0.0000 0.0000 endoplasmic reticulum 0.0000 0.0000 GO:0019882~antigen processing and presentation 0.0000 0.0000 hsa04612:Antigen processing and presentation 0.0000 0.0000 lysosome 0.0000 0.0000 SM00407:IGc1 0.0000 0.0000 IPR003597:Immunoglobulin C1-set 0.0000 0.0000 GO:0000323~lytic vacuole 0.0000 0.0000 GO:0005764~lysosome 0.0000 0.0000 signal 0.0000 0.0000 domain:Ig-like C1-type 0.0001 0.0001 GO:0005773~vacuole 0.0000 0.0001 GO:0006952~defense response 0.0001 0.0001 signal peptide 0.0001 0.0001 immune response 0.0000 0.0001 membrane 0.0001 0.0001 region of interest:Connecting peptide 0.0004 0.0003 GO:0005783~endoplasmic reticulum 0.0001 0.0004 GO:0042611~MHC protein complex 0.0001 0.0005 heterodimer 0.0016 0.0042 IPR003006:Immunoglobulin/major histocompatibility complex, conserved site 0.0034 0.0046 GO:0009611~response to wounding 0.0116 0.0079 GO:0044459~plasma membrane part 0.0031 0.0099 GO:0032395~MHC class II receptor activity 0.0059 0.0114 acetylated amino end 0.0050 0.0132 region of interest:Alpha-1 0.0163 0.0133 region of interest:Alpha-2 0.0163 0.0133 GO:0006954~inflammatory response 0.0206 0.0141 GO:0002504~antigen processing and presentation of peptide or polysaccharide antigen via MHC class II 0.0239 0.0164 hsa05330:Allograft rejection 0.0040 0.0282 mhc ii 0.0114 0.0302 GO:0048002~antigen processing and presentation of peptide antigen 0.0514 0.0358 GO:0042824~MHC class I peptide loading complex 0.0117 0.0373 phosphoprotein 0.0151 0.0403 GO:0009615~response to virus 0.0599 0.0419 hsa05332:Graft-versus-host disease 0.0085 0.0604 hsa04514:Cell adhesion molecules (CAMs) 0.0095 0.0670 GO:0044432~endoplasmic reticulum part 0.0250 0.0803 transmembrane 0.0351 0.0944 Supplement 4: GSEA Enrichment Analysis for Multivariate pSUV Model, q < 0.05 !"#$%&"'( )*++",$-*. /"."0"$1#2" 34#+%" !(5 !"#$%&% '()*+,!( '()*+,!(-*(..-*/*.(-!0+,+0* 123456(785 925:66(781 !"#$%&% '()*+,!( '()*+,!(-;0)<(+(=->)+?@)/= A2:539(78B 528AA5(781 !"#$%&% '()*+,!( '()*+,!(-!0+,+0*-!-!-C:->?)=(= 12649B(783 8288885:915 !"#$%&% D(CC D(CC-C.E+)+?0,F(-!(+)<,.0=! 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D9C<<;,O8> B9=C8:,O8B JLMNL%#" 0,*)/1?, 0,*)/1?,.?2/1/2).(01?,/*(7*!, =9=CB 898<;=ED JLMNL%#" 0,*)/1?, 0,*)/1?,.36*.!/0*63.,@16-*/216 89888D=CB< 898C<B 898;DDDD JLMNL%#" 0,*)/1?, 0,*)/1?,.*()3)C8.?,32*/,3.3,-0*3*/216.1G.)5)@26.4 8988<8CB> 898;;CE: JLMNL%#" +,-- +,--.*6/2-,6.(01),!!26-.*63.(0,!,6/*/216 89888;B;ED 898;E>DC JLMNL%#" +,-- +,--.),@@.)5)@, 89888;=8<> 898;E>DC JLMNL%#" 0,*)/1?, 0,*)/1?,.A6G1@3,3.(01/,26.0,!(16!, 8988CDC Supplement 5: Kaplan-Meier curves for single genes associated with FDG uptake features (external cohort) and survival (validation cohort)

LY6E RNF149

p=0.030 p=0.0002

MCM6 FAP

p=0.022 p=0.046

! Supplement 6. Survival analysis incorporating imaging features with known variables of prognosis in non-small cell lung cancer

External Cohort Validation Cohort Model Variable P-value Hazard Ratio CI Lower CI Upper P-value Hazard Ratio CI Lower CI Upper Clinical variables, Age 0.13 0.97 0.94 1.01 0.06 1.05 1.00 1.1 Univariate analysis Stage 0.00 1.95 1.31 2.90 0.02 2.83 1.19 6.7 Tumor size 0.03 1.21 1.02 1.44 0.04 1.26 1.01 1.6 Clinical variables, Age 0.95 1.00 0.96 1.04 0.01 1.07 1.02 1.1

Multivariate analysis Stage 0.01 1.81 1.17 2.80 0.23 2.03 0.64 6.4 Size 0.25 1.12 0.93 1.35 0.13 1.28 0.93 1.8 SUVmax and Age, Age 0.07 0.97 0.93 1.00 0.04 1.06 1.00 1.1 Bivariate analysis SUVmax 0.03 1.58 1.05 2.37 0.03 1.49 1.05 2.1 SUVmax and Stage, Stage 0.00 2.10 1.39 3.18 0.05 2.45 1.01 5.9 Bivariate analysis SUV 0.02 1.63 1.08 2.46 0.12 1.34 0.93 1.9 max SUVmax & Tumor size, Tumor size 0.03 1.23 1.02 1.48 0.13 1.20 0.95 1.5 Bivariate analysis SUVmax 0.04 1.49 1.02 2.17 0.18 1.28 0.89 1.8 SUVmax, Age, Stage, Age 0.66 0.99 0.95 1.03 0.01 1.08 1.02 1.1 and Tumor size, Stage 0.01 1.92 1.21 3.02 0.17 2.20 0.71 6.8 Multivariate analysis Tumor size 0.27 1.12 0.92 1.36 0.33 1.19 0.84 1.7

SUVmax 0.02 1.66 1.09 2.52 0.18 1.33 0.87 2.0 Multivariate-SUV and Age, Age 0.14 0.97 0.94 1.01 0.03 1.06 1.01 1.1

Bivariate analysis Multivariate-SUV 0.07 1.67 0.95 2.93 0.03 8.06 1.28 51.0 Muitivariate-SUV and Stage, Stage 0.00 1.91 1.29 2.83 0.11 2.10 0.84 5.3 Bivariate analysis Multivariate-SUV 0.09 1.66 0.92 2.98 0.18 3.82 0.54 27.0 Multivariate-SUV & Tumor size, Tumor size 0.06 1.18 0.99 1.41 0.25 1.16 0.90 1.5 Bivariate analysis Multivariate-SUV 0.13 1.55 0.88 2.71 0.21 3.53 0.48 26.0 Multivariate-SUV, Age, Age 0.94 1.00 0.96 1.04 0.01 1.08 1.02 1.1

Stage, and Tumor size, Stage 0.01 1.79 1.16 2.79 0.24 1.96 0.64 6.0 Multivariate analysis Tumor size 0.44 1.08 0.89 1.31 0.29 1.21 0.85 1.7 Multivariate-SUV 0.15 1.57 0.85 2.91 0.27 3.48 0.39 31.0

CI=95%confidence interval. Supplement 7: IPA networks for A) SUVmax and B) the multivariate-SUV model

A) Gene network for the pSUV max imaging feature !

! is quantified as the z-score (univariate SAM analysis) for each gene associated with overall survival in the external cohort. Green nodes are down-regulated genes, red nodes are up-regulated genes and white nodes are inferred in the network from the IPA database.

B) Gene network for the multivariate-pSUV imaging feature

Gene expression is quantified as the z-score (univariate SAM analysis) for each gene associated with overall survival in the external cohort. Green nodes are down-regulated genes, red nodes are up-regulated genes and white nodes are inferred in the network from the IPA database. ! ! !

! ! ! ! Supplement 8: Correlations for glycolytic pathway genes and SUVmax (Spearman-rank)

Gene Name rho* HIF1A hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) 0.55 PGK1 phosphoglycerate kinase 1 0.36 SLC2A1 solute carrier family 2 (facilitated glucose transporter), member 1 0.34 PFKFB3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 0.31 LDHA lactate dehydrogenase A 0.25 LDHB lactate dehydrogenase B 0.16 PKM2 pyruvate kinase, muscle 0.13 PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 0.09 GAPDH glyceraldehyde-3-phosphate dehydrogenase 0.03 VDAC1 porin -0.04 PFKP phosphofructokinase -0.05 ALDOA aldolase -0.12 ENO1 enolase -0.14

*rho=correlation coefficient

! ! !