Supplemental Figure 1

Supplemental Figure S1

Representative Hematoxylene and eosin stained cytospin preparations of a bronchial brushings

specimen from a healthy individual.

40x

10x

Supplemental Figure 2

Supplemental Figure S2

Quantitative measurements of selected proteins by PRM MS in a validation set of individual

bronchial brushing specimens. PRM MS results of 13 carbohydrate metabolic enzymes shown in

Figure 2B are not included. Two replicates of each specimen from low risk individuals were

compared to that of the high risk individuals.

Supplemental Figure 3

Supplemental Figure S3

Densitometry analysis of the Western blotting of metabolic enzymes. The ratio of the intensities of

enzyme bands and beta actin bands is presented. Open bars represent the intensities of the enzymes in

cultures treated with DMSO and closed bars represent the intensities of the enzymes in cultures treated

with CSC.

SupplementalTableS1.Characteristicsofindividualvolunteersprovidingbronchialbrushings.Group PtID Age Gender Smoking

statusLungCancerstatus

Histologysubtypeoflungcancer

Lowrisk

7036 55 Male Never No notapplicable7044 58 Female Never No notapplicable7071 60 Male Never No notapplicable7163 53 Male Never No notapplicable7143 65 Male Never No notapplicable

Mediumrisk

7030 64 Male Former No notapplicable7047 55 Male Former No notapplicable7178 59 Female Former No notapplicable7222 74 Female Former No notapplicable7228 45 Female Former No notapplicable

Highrisk

7018 68 Male Former No notapplicable7032 77 Female Former No notapplicable7089 68 Female Current No notapplicable7083 78 Male Former No notapplicable7072 68 Male Former No notapplicable

Neversmoker,Lungcancer

7448 56 Female Never Yes BronchioalveolarCarcinoma7485 59 Female Never Yes Adenocarcinoma7522 65 Male Never Yes Adenocarcinoma7617 80 Female Never Yes Adenocarcinoma7657 63 Female Never Yes Adenocarcinoma

Smoker,Lungcancer

7016 60 Male Former Yes LargeCellNeuroendocrine6820 59 Female Current Yes SquamousCellCarcinoma7080 72 Male Former Yes Adenocarcinoma7176 52 Female Current Yes LargeCellNeuroendocrine7182 85 Male Former Yes Adenocarcinoma7010 69 Female Former Yes SquamousCellCarcinoma7023 66 Male Former Yes SquamousCellCarcinoma7134 63 Male Current Yes Non-SmallCellLungCancer7053 68 Male Former Yes SquamousCellCarcinoma7116 77 Male Former Yes Adenocarcinoma

SupplementalTableS2.Numberofidentifiedproteingroupsandspectralcountsinriskgroups

RiskGroup DistinctPeptides Spectralcounts

ProteinGroups

Low 5,812 24,637 2,116 Medium 5,115 24,530 1,949 High 9,579 36,598 2,771

SupplementalTableS3.Numberofidentifiedproteingroupsandspectralcountsinthereplicatesofriskgroups

Riskgroups DistinctPeptidesSpectralcounts

ProteinGroups

Low 5,812 24,637 2,116Replicate1 4,218 9,036 1,689Replicate2 3,967 8,546 1,581Replicate3 3,127 7,055 1,357

Medium 5,115 24,530 1,949Replicate1 3,586 8,617 1,459Replicate2 3,835 9,419 1,531Replicate3 2,653 6,494 1,189

High 9,579 36,598 2,771Replicate1 6,697 13,153 2,316Replicate2 6,470 12,536 2,273Replicate3 5,674 10,909 2,046

SupplementalTableS4.ProteinsidentifiedbyshotgunproteomicanalysisdemonstratingsignificanttrenddirectionGenesymbol RefSeqID Proteinname Totalspectral

countTrendpvalue

Trenddirection

ACSF3 NP_777577 acyl-CoAsynthetasefamilymember3 1207 0.020 downACTN4 NP_004915 actinin,alpha4 405 0.035 upADSS NP_001117 adenylosuccinatesynthase 22 0.035 upAKR1B10 NP_064695 aldo-ketoreductasefamily1,memberB10

(aldosereductase)27 0.046 up

ALDH1A1 NP_000680 aldehydedehydrogenase1family,memberA1

179 0.035 up

ALDH3A1 NP_000682 aldehydedehydrogenase3family,memberA1

268 0.035 up

ALOX15 NP_001131 arachidonate15-lipoxygenase 323 0.011 downANP32A NP_006296 acidic(leucine-rich)nuclearphosphoprotein

32family,memberA40 0.020 up

ANXA2 NP_001129487 annexinA2 1262 0.035 downANXA3 NP_005130 annexinA3 74 0.020 upANXA6 NP_001146 annexinA6 109 0.011 upANXA8L2 NP_001621 annexinA8-like2 7 0.046 upAP1B1 NP_663782 adaptor-relatedproteincomplex1,beta1

subunit28 0.020 up

AP2B1 NP_001273 adaptor-relatedproteincomplex2,beta1subunit

23 0.020 up

ARCN1 NP_001646 archain1 5 0.046 upARF3 NP_001650 ADP-ribosylationfactor3 36 0.011 upARF5 NP_001653 ADP-ribosylationfactor5 13 0.046 upARFGAP2 NP_115765 ADP-ribosylationfactorGTPaseactivating

protein28 0.046 up

ARFGAP3 NP_055385 ADP-ribosylationfactorGTPaseactivatingprotein3

7 0.046 up

ARFIP2 NP_001229783 ADP-ribosylationfactorinteractingprotein2 8 0.046 upASS1 NP_446464 argininosuccinatesynthase1 13 0.046 upATP12A NP_001667 ATPase,H+/K+transporting,nongastric,

alphapolypeptide7 0.046 up

ATP5D NP_001678 ATPsynthase,H+transporting,mitochondrialF1complex,deltasubunit

109 0.011 down

ATP5O NP_001688 ATPsynthase,H+transporting,mitochondrialF1complex,Osubunit

28 0.035 up

BAG3 NP_004272 BCL2-associatedathanogene3 5 0.046 upBAG5 NP_001015048 BCL2-associatedathanogene5 5 0.046 upBANF1 NP_003851 barriertoautointegrationfactor1 6 0.046 upBAX NP_004315 BCL2-associatedXprotein 7 0.046 upBBS2 NP_114091 Bardet-Biedlsyndrome2 9 0.035 upBCAM NP_005572 basalcelladhesionmolecule(Lutheran

bloodgroup)38 0.035 up

BCAS1 NP_003648 breastcarcinomaamplifiedsequence1 27 0.020 upBNIP1 NP_001196 BCL2/adenovirusE1B19kDainteracting

protein16 0.046 up

BRCA2 NP_000050 breastcancer2,earlyonset 3771 0.035 downBRK1 NP_060932 BRICK1,SCAR/WAVEactin-nucleating

complexsubunit7 0.046 up

C14orf166 NP_057123 chromosome14openreadingframe166 16 0.046 upC1orf31 NP_001193570 chromosome1openreadingframe31 15 0.026 upC1orf87 NP_689590 chromosome1openreadingframe87 44 0.035 downC9orf142 NP_899064 chromosome9openreadingframe142 11 0.046 upC9orf171 NP_997300 chromosome9openreadingframe171 13 0.026 upCALU NP_001186601 calumenin 31 0.011 upCAND1 NP_060918 cullin-associatedandneddylation-

dissociated174 0.035 up

CAND2 NP_036430 cullin-associatedandneddylation-dissociated2(putative)

7 0.046 up

CAPN1 NP_005177 calpain1,(mu/I)largesubunit 77 0.020 upCAPN2 NP_001739 calpain2,(m/II)largesubunit 41 0.035 upCAPS NP_004049 calcyphosine 570 0.020 upCBR1 NP_001748 carbonylreductase1 57 0.035 upCBR3 NP_001227 carbonylreductase3 25 0.026 upCCDC113 NP_054876 coiled-coildomaincontaining113 3 0.046 upCCDC17 NP_001108410 coiled-coildomaincontaining17 24 0.011 downCCT6A NP_001753 chaperonincontainingTCP1,subunit6A

(zeta1)104 0.035 up

CCT7 NP_006420 chaperonincontainingTCP1,subunit7(eta) 29 0.008 upCD2AP NP_036252 CD2-associatedprotein 6 0.046 upCDC37 NP_008996 celldivisioncycle37homolog(S.cerevisiae) 7 0.035 upCDIPT NP_006310 CDP-diacylglycerol--inositol3-

phosphatidyltransferase7 0.046 up

CEACAM5 NP_004354 carcinoembryonicantigen-relatedcelladhesionmolecule5

32 0.046 up

CETN2 NP_004335 centrin,EF-handprotein,2 38 0.046 upCHCHD1 NP_976043 coiled-coil-helix-coiled-coil-helixdomain

containing13 0.046 up

CHCHD3 NP_060282 coiled-coil-helix-coiled-coil-helixdomaincontaining3

88 0.005 up

CHCHD6 NP_115719 coiled-coil-helix-coiled-coil-helixdomaincontaining6

3 0.046 up

CLMN NP_079010 calmin(calponin-like,transmembrane) 14 0.035 downCLTA NP_001171690 clathrin,lightchainA 33 0.035 upCORO1B NP_065174 coronin,actinbindingprotein,1B 23 0.046 upCOX2 YP_003024029 cytochromecoxidasesubunitII 100 0.035 upCPOX NP_000088 coproporphyrinogenoxidase 8 0.046 upCRAT NP_000746 carnitineO-acetyltransferase 14 0.020 upCSNK2A2 NP_001887 caseinkinase2,alphaprimepolypeptide 3 0.046 upCTBP1 NP_001319 C-terminalbindingprotein1 10 0.046 upCUX1 NP_852477 cut-likehomeobox1 14 0.011 downCYP1A1 NP_000490 cytochromeP450,family1,subfamilyA,

polypeptide16 0.046 up

CYP1B1 NP_000095 cytochromeP450,family1,subfamilyB, 16 0.046 up

polypeptide1DCAF12L1 NP_848565 DDB1andCUL4associatedfactor12-like1 13 0.035 downDCTN4 NP_057305 dynactin4(p62) 3773 0.035 downDCXR NP_057370 dicarbonyl/L-xylulosereductase 8 0.046 upDDI2 NP_115717 DNA-damageinducible1homolog2(S.

cerevisiae)19 0.046 up

DEFA1B NP_001035965 defensin,alpha1B 175 0.003 downDGKA NP_963848 diacylglycerolkinase,alpha80kDa 4 0.046 upDHX9 NP_001348 DEAH(Asp-Glu-Ala-His)boxpolypeptide9 87 0.035 downDIP2B NP_775873 DIP2disco-interactingprotein2homologB

(Drosophila)24 0.046 up

DLG5 NP_004738 discs,largehomolog5(Drosophila) 90 0.011 downDLST NP_001924 dihydrolipoamideS-succinyltransferase(E2

componentof2-oxo-glutaratecomplex)92 0.011 up

DNAH5 NP_001360 dynein,axonemal,heavychain5 263 0.035 downDNAJA1 NP_001530 DnaJ(Hsp40)homolog,subfamilyA,

member124 0.020 down

DNAJB1 NP_006136 DnaJ(Hsp40)homolog,subfamilyB,member1

11 0.046 up

DPP7 NP_037511 dipeptidyl-peptidase7 14 0.046 upDPYSL3 NP_001184223 dihydropyrimidinase-like3 18 0.020 upDYNC1H1 NP_001367 dynein,cytoplasmic1,heavychain1 255 0.011 upDYNC1LI1 NP_057225 dynein,cytoplasmic1,lightintermediate

chain122 0.011 up

EFHD2 NP_077305 EF-handdomainfamily,memberD2 27 0.020 upEIF3F NP_003745 eukaryotictranslationinitiationfactor3,

subunitF9 0.046 up

EIF5 NP_001960 eukaryotictranslationinitiationfactor5 10 0.046 upEML2 NP_036287 echinodermmicrotubuleassociatedprotein

like223 0.005 up

EML4 NP_061936 echinodermmicrotubuleassociatedproteinlike4

28 0.003 up

FAF2 NP_055428 Fasassociatedfactorfamilymember2 8 0.046 upFAM213A NP_001230707 familywithsequencesimilarity213,

memberA6 0.046 up

FASN NP_004095 fattyacidsynthase 40 0.005 upFBLN1 NP_006477 fibulin1 10 0.046 upFGA NP_000499 fibrinogenalphachain 2598 0.005 downFGB NP_005132 fibrinogenbetachain 1313 0.003 downFGG NP_000500 fibrinogengammachain 1318 0.035 downFNTA NP_002018 farnesyltransferase,CAAXbox,alpha 5 0.046 upFTH1 NP_002023 ferritin,heavypolypeptide1 37 0.011 upFUBP3 NP_003925 farupstreamelement(FUSE)binding

protein35 0.046 up

GADD45GIP1 NP_443082 growtharrestandDNA-damage-inducible,gammainteractingprotein1

6 0.046 up

GALNT12 NP_078918 UDP-N-acetyl-alpha-D-galactosamine:polypeptideN-

9 0.020 up

acetylgalactosaminyltransferase12(GalNAc-T12)

GBA NP_001005742 glucosidase,beta,acid 9 0.046 upGCLC NP_001489 glutamate-cysteineligase,catalyticsubunit 11 0.046 upGDI1 NP_001484 GDPdissociationinhibitor1 21 0.035 upGDI2 NP_001485 GDPdissociationinhibitor2 59 0.011 upGLB1 NP_000395 galactosidase,beta1 11 0.046 upGLIPR2 NP_071738 GLIpathogenesis-related2 42 0.026 downGLTSCR1 NP_056526 gliomatumorsuppressorcandidateregion

gene15 0.035 down

GMDS NP_001491 GDP-mannose4,6-dehydratase 16 0.015 upGNA11 NP_002058 guaninenucleotidebindingprotein(G

protein),alpha11(Gqclass)19 0.035 up

GNAI2 NP_002061 guaninenucleotidebindingprotein(Gprotein),alphainhibitingactivitypolypeptide2

76 0.035 up

GOLM1 NP_057632 golgimembraneprotein1 42 0.035 upGSN NP_001121134 gelsolin 141 0.035 upH1F0 NP_005309 H1histonefamily,member0 185 0.035 downH2AFV NP_036544 H2Ahistonefamily,memberV 73 0.035 downHARS2 NP_036340 histidyl-tRNAsynthetase2,mitochondrial 4 0.046 upHBE1 NP_005321 hemoglobin,epsilon1 58 0.003 downHBG1 NP_000550 hemoglobin,gammaA 191 0.020 downHIST1H1C NP_005310 histonecluster1,H1c 700 0.020 downHIST1H1D NP_005311 histonecluster1,H1d 484 0.035 downHIST1H1E NP_005312 histonecluster1,H1e 688 0.035 downHIST1H2AC NP_003503 histonecluster1,H2ac 401 0.020 downHIST1H4D NP_003530 histonecluster1,H4d 1210 0.035 downHLA-DRB1 NP_002115 majorhistocompatibilitycomplex,classII,

DRbeta157 0.020 up

HMGCS2 NP_005509 3-hydroxy-3-methylglutaryl-CoAsynthase2(mitochondrial)

8 0.046 up

HP1BP3 NP_057371 heterochromatinprotein1,bindingprotein3

71 0.003 up

HSP90AA1 NP_001017963 heatshockprotein90kDaalpha(cytosolic),classAmember1

825 0.035 up

HSP90AB1 NP_031381 heatshockprotein90kDaalpha(cytosolic),classBmember1

820 0.020 up

HSPA4 NP_002145 heatshock70kDaprotein4 66 0.020 upHSPE1 NP_002148 heatshock10kDaprotein1(chaperonin10) 113 0.035 downHSPH1 NP_006635 heatshock105kDa/110kDaprotein1 90 0.020 upIDH1 NP_005887 isocitratedehydrogenase1(NADP+),soluble 55 0.011 upIDH2 NP_002159 isocitratedehydrogenase2(NADP+),

mitochondrial193 0.035 up

IFT122 NP_443715 intraflagellartransport122homolog(Chlamydomonas)

6 0.046 up

IFT81 NP_001137251 intraflagellartransport81homolog(Chlamydomonas)

15 0.046 up

IGF2BP2 NP_006539 insulin-likegrowthfactor2mRNAbindingprotein2

8 0.046 up

IMPA1 NP_005527 inositol(myo)-1(or4)-monophosphatase1 12 0.026 upITIH1 NP_002206 inter-alpha-trypsininhibitorheavychain1 21 0.026 upKARS NP_005539 lysyl-tRNAsynthetase 52 0.020 upKIAA1324 NP_065826 KIAA1324 5 0.046 upKIF1C NP_006603 kinesinfamilymember1C 7 0.046 upKIF5B NP_004512 kinesinfamilymember5B 76 0.035 upKIF9 NP_001128350 kinesinfamilymember9 5 0.046 upKRT1 NP_006112 keratin1 1385 0.003 downKRT10 NP_000412 keratin10 887 0.003 downKRT17 NP_000413 keratin17 2644 0.020 downKRT2 NP_000414 keratin2 677 0.035 downKRT31 NP_002268 keratin31 84 0.035 downKRT33B NP_002270 keratin33B 68 0.035 downKRT34 NP_066293 keratin34 72 0.035 downKRT36 NP_003762 keratin36 28 0.046 downKRT38 NP_006762 keratin38 14 0.020 downKRT7 NP_005547 keratin7 1413 0.005 downKRT79 NP_787028 keratin79 306 0.020 downKRT8 NP_002264 keratin8 4203 0.005 downKRT83 NP_002273 keratin83 88 0.003 downKRT85 NP_002274 keratin85 94 0.005 downKRT86 NP_002275 keratin86 107 0.003 downLBR NP_919424 laminBreceptor 9 0.035 upLCORL NP_710153 liganddependentnuclearreceptor

corepressor-like60 0.035 down

LDHB NP_002291 lactatedehydrogenaseB 163 0.020 upLGALS7B NP_001035972 lectin,galactoside-binding,soluble,7B 62 0.020 upLIMK1 NP_002305 LIMdomainkinase1 5 0.046 downLLGL2 NP_001026973 lethalgiantlarvaehomolog2(Drosophila) 17 0.035 upLMO7 NP_005349 LIMdomain7 13 0.026 upLRRFIP1 NP_004726 leucinerichrepeat(inFLII)interacting

protein133 0.005 up

LRRFIP2 NP_006300 leucinerichrepeat(inFLII)interactingprotein2

11 0.046 up

LSS NP_002331 lanosterolsynthase(2,3-oxidosqualene-lanosterolcyclase)

25 0.020 up

LUZP1 NP_361013 leucinezipperprotein1 3 0.046 upLYN NP_002341 v-yes-1Yamaguchisarcomaviralrelated

oncogenehomolog11 0.046 up

MAN2A1 NP_002363 mannosidase,alpha,class2A,member1 6 0.035 upMANF NP_006001 mesencephalicastrocyte-derived

neurotrophicfactor31 0.020 up

MAOA NP_000231 monoamineoxidaseA 43 0.020 upMBOAT7 NP_001139555 membraneboundO-acyltransferasedomain

containing714 0.020 up

MCU NP_612366 mitochondrialcalciumuniporter 10 0.046 up

ME2 NP_002387 malicenzyme2,NAD(+)-dependent,mitochondrial

32 0.020 up

MKRN3 NP_005655 makorinringfingerprotein3 51 0.046 downMLF1 NP_001123629 myeloidleukemiafactor1 29 0.035 downMOGS NP_006293 mannosyl-oligosaccharideglucosidase 16 0.046 upMRPL43 NP_115488 mitochondrialribosomalproteinL43 35 0.035 downMSH6 NP_000170 mutShomolog6(E.coli) 3 0.046 upMSN NP_002435 moesin 107 0.020 upMTHFD1 NP_005947 methylenetetrahydrofolatedehydrogenase

(NADP+dependent)1,methenyltetrahydrofolatecyclohydrolase,formyltetrahydrofolatesynthetase

15 0.015 up

MVP NP_005106 majorvaultprotein 240 0.035 upMYH10 NP_001242941 myosin,heavychain10,non-muscle 89 0.003 upMYH9 NP_002464 myosin,heavychain9,non-muscle 691 0.003 upMYL1 NP_524146 myosin,lightchain1,alkali;skeletal,fast 22 0.020 upMYL6 NP_524147 myosin,lightchain6,alkali,smoothmuscle

andnon-muscle195 0.005 up

MYO1C NP_203693 myosinIC 15 0.003 up

NAE1 NP_003896 NEDD8activatingenzymeE1subunit1 5 0.046 up

NCL NP_005372 nucleolin 97 0.035 upNDUFAF3 NP_951032 NADHdehydrogenase(ubiquinone)complex

I,assemblyfactor36 0.046 up

NDUFV1 NP_001159574 NADHdehydrogenase(ubiquinone)flavoprotein1,51kDa

16 0.026 up

NFKB1 NP_003989 nuclearfactorofkappalightpolypeptidegeneenhancerinB-cells1

8 0.046 up

NLRP12 NP_653288 NLRfamily,pyrindomaincontaining12 22 0.003 downNUP85 NP_079120 nucleoporin85kDa 7 0.046 upOAS1 NP_001027581 2'-5'-oligoadenylatesynthetase1,40/46kDa 1201 0.020 downODF2L NP_065780 outerdensefiberofspermtails2-like 14 0.035 upOPA1 NP_056375 opticatrophy1(autosomaldominant) 25 0.035 upPACSIN3 NP_057307 proteinkinaseCandcaseinkinasesubstrate

inneurons38 0.046 up

PAFAH1B1 NP_000421 platelet-activatingfactoracetylhydrolase1b,regulatorysubunit1(45kDa)

4 0.046 up

PBLD NP_071412 phenazinebiosynthesis-likeproteindomaincontaining

12 0.046 up

PCCA NP_000273 propionylCoAcarboxylase,alphapolypeptide

18 0.026 up

PCYT1B NP_004836 phosphatecytidylyltransferase1,choline,beta

11 0.046 up

PDLIM4 NP_003678 PDZandLIMdomain4 9 0.035 upPEBP1 NP_002558 phosphatidylethanolaminebindingprotein1 86 0.020 upPFKL NP_002617 phosphofructokinase,liver 9 0.046 up

PFKP NP_002618 phosphofructokinase,platelet 23 0.020 upPGD NP_002622 phosphogluconatedehydrogenase 134 0.020 upPGK1 NP_000282 phosphoglyceratekinase1 113 0.020 upPGM1 NP_002624 phosphoglucomutase1 13 0.020 upPIR NP_001018119 pirin(iron-bindingnuclearprotein) 6 0.046 upPITRM1 NP_055704 pitrilysinmetallopeptidase1 22 0.020 upPKM NP_002645 pyruvatekinase,muscle 318 0.003 upPKP3 NP_009114 plakophilin3 29 0.020 upPLSCR1 NP_066928 phospholipidscramblase1 10 0.046 upPOF1B NP_079197 prematureovarianfailure,1B 18 0.035 downPOR NP_000932 P450(cytochrome)oxidoreductase 23 0.035 downPPIF NP_005720 peptidylprolylisomeraseF 20 0.046 upPPIH NP_006338 peptidylprolylisomeraseH(cyclophilinH) 7 0.046 upPPIL1 NP_057143 peptidylprolylisomerase(cyclophilin)-like1 6 0.046 upPPP2R4 NP_066954 proteinphosphatase2Aactivator,

regulatorysubunit412 0.026 up

PPP2R5E NP_006237 proteinphosphatase2,regulatorysubunitB',epsilonisoform

7 0.046 up

PRB3 NP_006240 proline-richproteinBstNIsubfamily3 9 0.026 upPRDX6 NP_004896 peroxiredoxin6 104 0.035 upPRMT1 NP_001527 proteinargininemethyltransferase1 13 0.046 downPRPF6 NP_036601 PRP6pre-mRNAprocessingfactor6

homolog(S.cerevisiae)10 0.046 up

PSMD13 NP_002808 proteasome(prosome,macropain)26Ssubunit,non-ATPase,13

15 0.020 up

PSMD6 NP_055629 proteasome(prosome,macropain)26Ssubunit,non-ATPase,6

12 0.035 up

PTCD3 NP_060422 pentatricopeptiderepeatdomain3 6 0.046 upPTGES2 NP_079348 prostaglandinEsynthase2 4 0.046 upPYGB NP_002853 phosphorylase,glycogen;brain 28 0.026 upRAB21 NP_055814 RAB21,memberRASoncogenefamily 10 0.046 upRABAC1 NP_006414 Rabacceptor1(prenylated) 8 0.046 upRAD23B NP_002865 RAD23homologB(S.cerevisiae) 25 0.008 upRBBP4 NP_001128728 retinoblastomabindingprotein4 30 0.020 upRBMXL1 NP_062556 RNAbindingmotifprotein,X-linked-like1 184 0.035 downRGPD3 NP_001137485 RANBP2-likeandGRIPdomaincontaining3 83 0.035 downRHOB NP_004031 rashomologfamilymemberB 22 0.035 upRPL11 NP_000966 ribosomalproteinL11 32 0.011 upRPL14 NP_003964 ribosomalproteinL14 60 0.035 upRPL27 NP_000979 ribosomalproteinL27 43 0.035 upRPL27A NP_000981 ribosomalproteinL27a 18 0.026 downRPL5 NP_000960 ribosomalproteinL5 16 0.046 upRPS13 NP_001008 ribosomalproteinS13 102 0.020 downRPS16 NP_001011 ribosomalproteinS16 18 0.020 upRPS19 NP_001013 ribosomalproteinS19 66 0.020 upRPS4X NP_000998 ribosomalproteinS4,X-linked 30 0.011 downRSPH9 NP_689945 radialspokehead9homolog 55 0.011 down

(Chlamydomonas)S100A2 NP_005969 S100calciumbindingproteinA2 16 0.035 upSCGB1A1 NP_003348 secretoglobin,family1A,member1

(uteroglobin)189 0.020 down

SCRIB NP_874365 scribbledhomolog(Drosophila) 11 0.046 upSEC62 NP_003253 SEC62homolog(S.cerevisiae) 4 0.046 upSERPINB1 NP_109591 serpinpeptidaseinhibitor,cladeB

(ovalbumin),member1109 0.035 up

SF3A3 NP_006793 splicingfactor3a,subunit3,60kDa 16 0.046 upSF3B14 NP_057131 splicingfactor3B,14kDasubunit 11 0.035 upSFN NP_006133 stratifin 35 0.008 upSFTPB NP_000533 surfactantproteinB 45 0.003 downSH3GL1 NP_001186872 SH3-domainGRB2-like1 6 0.046 upSH3GLB2 NP_064530 SH3-domainGRB2-likeendophilinB2 7 0.046 upSHROOM3 NP_065910 shroomfamilymember3 25 0.046 downSIRT5 NP_112534 sirtuin5 13 0.020 upSLC25A11 NP_003553 solutecarrierfamily25(mitochondrial

carrier;oxoglutaratecarrier),member1120 0.011 down

SMARCC2 NP_001123892 SWI/SNFrelated,matrixassociated,actindependentregulatorofchromatin,subfamilyc,member2

7 0.046 up

SMARCE1 NP_003070 SWI/SNFrelated,matrixassociated,actindependentregulatorofchromatin,subfamilye,member1

13 0.046 up

SMC4 NP_005487 structuralmaintenanceofchromosomes4 31 0.003 downSNRPA1 NP_003081 smallnuclearribonucleoproteinpolypeptide

A'14 0.020 down

SNX6 NP_689419 sortingnexin6 6 0.046 upSPRYD4 NP_997227 SPRYdomaincontaining4 11 0.046 upSRP54 NP_003127 signalrecognitionparticle54kDa 13 0.046 upSRP68 NP_055045 signalrecognitionparticle68kDa 13 0.046 upSTIP1 NP_006810 stress-induced-phosphoprotein1 49 0.003 upSTT3A NP_689926 STT3,subunitofthe

oligosaccharyltransferasecomplex,homologA(S.cerevisiae)

40 0.035 up

STUB1 NP_005852 STIP1homologyandU-boxcontainingprotein1,E3ubiquitinproteinligase

6 0.046 up

SUGT1 NP_001124384 SGT1,suppressorofG2alleleofSKP1(S.cerevisiae)

15 0.035 up

TBL2 NP_036585 transducin(beta)-like2 4 0.046 upTCERG1 NP_006697 transcriptionelongationregulator1 169 0.003 downTEKT1 NP_444515 tektin1 75 0.035 upTIAL1 NP_001029097 TIA1cytotoxicgranule-associatedRNA

bindingprotein-like110 0.035 up

TM2D3 NP_510883 TM2domaincontaining3 1200 0.020 downTMEM231 NP_001070884 transmembraneprotein231 24 0.035 downTMEM48 NP_060557 transmembraneprotein48 4 0.046 upTMX4 NP_066979 thioredoxin-relatedtransmembraneprotein 8 0.046 up

4TNPO1 NP_002261 transportin1 24 0.035 upTOP2B NP_001059 topoisomerase(DNA)IIbeta180kDa 32 0.046 upTPGS1 NP_277048 tubulinpolyglutamylasecomplexsubunit1 7 0.046 upTPM3 NP_705935 tropomyosin3 225 0.035 upTRA2B NP_001230808 transformer2betahomolog(Drosophila) 4 0.046 upTRIM2 NP_056086 tripartitemotifcontaining2 11 0.046 upTST NP_003303 thiosulfatesulfurtransferase(rhodanese) 15 0.046 upTUBA1A NP_006000 tubulin,alpha1a 655 0.020 downTUBB1 NP_110400 tubulin,beta1classVI 199 0.035 downTUBGCP3 NP_006313 tubulin,gammacomplexassociatedprotein

37 0.046 up

UBA1 NP_695012 ubiquitin-likemodifieractivatingenzyme1 189 0.035 upUCHL3 NP_005993 ubiquitincarboxyl-terminalesteraseL3

(ubiquitinthiolesterase)8 0.046 up

UFSP2 NP_060829 UFM1-specificpeptidase2 10 0.046 upUGP2 NP_006750 UDP-glucosepyrophosphorylase2 16 0.020 upUHRF1BP1L NP_055869 UHRF1bindingprotein1-like 110 0.011 downUNC45A NP_061141 unc-45homologA(C.elegans) 7 0.046 upUPK3BL NP_001107875 uroplakin3B-like 7 0.046 upUQCRH NP_005995 ubiquinol-cytochromecreductasehinge

protein5 0.046 up

VAMP2 NP_055047 vesicle-associatedmembraneprotein2(synaptobrevin2)

16 0.035 up

VPS28 NP_057292 vacuolarproteinsorting28homolog(S.cerevisiae)

7 0.046 up

WARS NP_004175 tryptophanyl-tRNAsynthetase 47 0.015 upWDR35 NP_065830 WDrepeatdomain35 12 0.046 upXPO1 NP_003391 exportin1(CRM1homolog,yeast) 15 0.008 upXRN2 NP_036387 5'-3'exoribonuclease2 7 0.046 upYWHAH NP_003396 tyrosine3-monooxygenase/tryptophan5-

monooxygenaseactivationprotein,etapolypeptide

82 0.011 up

ZNF281 NP_036614 zincfingerprotein281 30 0.020 down

SupplementalTableS5.Enrichedpathwaysfromshotgunproteomicsdata GenesymbolProteinMetabolicpathways 1 UGP2 UDP-glucosepyrophosphorylase22 PRDX6 peroxiredoxin63 PCYT1B phosphatecytidylyltransferase1,choline,beta4 PAFAH1B1 platelet-activatingfactoracetylhydrolase1b,regulatorysubunit1(45kDa)5 GALNT12 UDP-N-acetyl-alpha-D-galactosamine:polypeptideN-acetylgalactosaminyltransferase 12 (GalNAc-T12)6 DGKA diacylglycerolkinase,alpha80kDa7 MOGS mannosyl-oligosaccharideglucosidase8 ASS1 argininosuccinatesynthase19 IDH2 isocitratedehydrogenase2(NADP+),mitochondrial10 CDIPT CDP-diacylglycerol--inositol3-phosphatidyltransferase11 ALOX15 arachidonate15-lipoxygenase12 NDUFV1 NADHdehydrogenase(ubiquinone)flavoprotein1,51kDa13 CYP1A1 cytochromeP450,family1,subfamilyA,polypeptide114 PFKL phosphofructokinase,liver15 ALDH3A1 aldehydedehydrogenase3family,memberA116 MAN2A1 mannosidase,alpha,class2A,member117 GMDS GDP-mannose4,6-dehydratase18 LDHB lactatedehydrogenaseB19 MTHFD1 methylenetetrahydrofolatedehydrogenase(NADP+dependent)1,methenyltetrahydrofolate cyclohydrolase,formyltetrahydrofolatesynthetase20 IMPA1 inositol(myo)-1(or4)-monophosphatase121 PGM1 phosphoglucomutase122 GCLC glutamate-cysteineligase,catalyticsubunit23 PCCA propionylCoAcarboxylase,alphapolypeptide24 CPOX coproporphyrinogenoxidase25 AKR1B10 aldo-ketoreductasefamily1,memberB10(aldosereductase)26 FASN fattyacidsynthase27 GBA glucosidase,beta,acid28 HMGCS2 3-hydroxy-3-methylglutaryl-CoAsynthase2(mitochondrial)29 PKM pyruvatekinase,muscle30 DLST dihydrolipoamideS-succinyltransferase(E2componentof2-oxo-glutaratecomplex)31 IDH1 isocitratedehydrogenase1(NADP+),soluble32 PTGES2 prostaglandinEsynthase233 ATP5D ATPsynthase,H+transporting,mitochondrialF1complex,deltasubunit34 TST thiosulfatesulfurtransferase(rhodanese)35 PGD phosphogluconatedehydrogenase36 ADSS adenylosuccinatesynthase37 LSS lanosterolsynthase(2,3-oxidosqualene-lanosterolcyclase)38 CBR1 carbonylreductase139 PGK1 phosphoglyceratekinase140 DCXR dicarbonyl/L-xylulosereductase41 STT3A STT3,subunitoftheoligosaccharyltransferasecomplex,homologA(S.cerevisiae)42 MAOA monoamineoxidaseA43 GLB1 galactosidase,beta144 UQCRH ubiquinol-cytochromecreductasehingeprotein45 CBR3 carbonylreductase3

46 ALDH1A1 aldehydedehydrogenase1family,memberA147 ATP5O ATPsynthase,H+transporting,mitochondrialF1complex,Osubunit48 PFKP phosphofructokinase,plateletProteinprocessinginendoplasmicreticulum 1 CAPN2 calpain2,(m/II)largesubunit2 STUB1 STIP1homologyandU-boxcontainingprotein1,E3ubiquitinproteinligase3 HSPH1 heatshock105kDa/110kDaprotein14 STT3A STT3,subunitoftheoligosaccharyltransferasecomplex,homologA(S.cerevisiae)5 HSP90AB1 heatshockprotein90kDaalpha(cytosolic),classBmember16 SEC62 SEC62homolog(S.cerevisiae)7 RAD23B RAD23homologB(S.cerevisiae)8 BAX BCL2-associatedXprotein9 MOGS mannosyl-oligosaccharideglucosidase10 HSP90AA1 heatshockprotein90kDaalpha(cytosolic),classAmember111 DNAJB1 DnaJ(Hsp40)homolog,subfamilyB,member112 DNAJA1 DnaJ(Hsp40)homolog,subfamilyA,member113 CAPN1 calpain1,(mu/I)largesubunitRibosome 1 RPS4X ribosomalproteinS4,X-linked2 RPS16 ribosomalproteinS163 RPL27 ribosomalproteinL274 RPS19 ribosomalproteinS195 RPL14 ribosomalproteinL146 RPL27A ribosomalproteinL27a7 RPL5 ribosomalproteinL58 RPL11 ribosomalproteinL119 RPS13 ribosomalproteinS13Galactosemetabolism 1 GLB1 galactosidase,beta12 PGM1 phosphoglucomutase13 UGP2 UDP-glucosepyrophosphorylase24 PFKL phosphofructokinase,liver5 PFKP phosphofructokinase,plateletGlycolysis/Gluconeogenesis 1 PGM1 phosphoglucomutase12 PKM pyruvatekinase,muscle3 PGK1 phosphoglyceratekinase14 PFKL phosphofructokinase,liver5 ALDH3A1 aldehydedehydrogenase3family,memberA16 PFKP phosphofructokinase,platelet7 LDHB lactatedehydrogenaseB Spliceosome 1 SNRPA1 smallnuclearribonucleoproteinpolypeptideA'2 SF3B14 splicingfactor3B,14kDasubunit3 TRA2B transformer2betahomolog(Drosophila)

4 SF3A3 splicingfactor3a,subunit3,60kDa5 PPIL1 peptidylprolylisomerase(cyclophilin)-like16 PPIH peptidylprolylisomeraseH(cyclophilinH)7 PRPF6 PRP6pre-mRNAprocessingfactor6homolog(S.cerevisiae)8 TCERG1 transcriptionelongationregulator19 RBMXL1 RNAbindingmotifprotein,X-linked-like1 Pentosephosphatepathway 1 PGM1 phosphoglucomutase12 PFKL phosphofructokinase,liver3 PFKP phosphofructokinase,platelet4 PGD phosphogluconatedehydrogenase Fructoseandmannosemetabolism 1 GMDS GDP-mannose4,6-dehydratase2 PFKL phosphofructokinase,liver3 PFKP phosphofructokinase,platelet4 AKR1B10 aldo-ketoreductasefamily1,memberB10(aldosereductase)Phenylalaninemetabolism 1 MAOA monoamineoxidaseA2 PRDX6 peroxiredoxin63 ALDH3A1 aldehydedehydrogenase3family,memberA1Tryptophanmetabolism 1 MAOA monoamineoxidaseA2 CYP1A1 cytochromeP450,family1,subfamilyA,polypeptide13 WARS tryptophanyl-tRNAsynthetase4 CYP1B1 cytochromeP450,family1,subfamilyB,polypeptide1Vasopressin-regulatedwaterreabsorption 1 DYNC1H1 dynein,cytoplasmic1,heavychain12 VAMP2 vesicle-associatedmembraneprotein2(synaptobrevin2)3 DYNC1LI1 dynein,cytoplasmic1,lightintermediatechain14 DCTN4 dynactin4(p62)Proteinexport 1 SRP54 signalrecognitionparticle54kDa2 SRP68 signalrecognitionparticle68kDa3 SEC62 SEC62homolog(S.cerevisiae)Huntington'sdisease 1 AP2B1 adaptor-relatedproteincomplex2,beta1subunit2 CLTA clathrin,lightchainA3 UQCRH ubiquinol-cytochromecreductasehingeprotein4 NDUFV1 NADHdehydrogenase(ubiquinone)flavoprotein1,51kDa5 ATP5O ATPsynthase,H+transporting,mitochondrialF1complex,Osubunit6 DCTN4 dynactin4(p62)7 BAX BCL2-associatedXprotein8 ATP5D ATPsynthase,H+transporting,mitochondrialF1complex,deltasubunit

Glutathionemetabolism 1 IDH2 isocitratedehydrogenase2(NADP+),mitochondrial2 IDH1 isocitratedehydrogenase1(NADP+),soluble3 GCLC glutamate-cysteineligase,catalyticsubunit4 PGD phosphogluconatedehydrogenase

SupplementalTableS6:SelectedcandidatesforvalidationbyParallelReactionMonitoringMassSpectrometry

Candidate Criteriaforselection:pathways;datasetfrompreviousstudies Trendpvalue up/downACSF3 Lipidmetabolism 0.0196 downALDH1A1 Alcoholandaldehydemetabolism;1Massion,MCP 0.0348 upALDH3A1 Alcoholandaldehydemetabolism;Massion,MCP;Crystal,BMC,Spira,PNAS0.0348 upALOX15 Lipidmetabolism 0.0106 downANXA2 Massion,MCP;Crystal,BMC 0.0348 downANXA3 Massion,MCP;Spira,PNAS 0.0196 upANXA6 Massion,MCP 0.0106 upCEACAM5 Cancerbiomarker;Massion,MCP 0.0455 upDLST Carbohydratemetabolism 0.0106 upEML4 Absentincontrol.EML4/ALKtranslocationinNSCLC;Massion,MCP 0.0027 upFASN Lipidmetabolism;Massion,MCP 0.0055 upGLB1 Carbohydratemetabolism 0.0455 upHSP90AA1 candidatebiomarker,ATPaseactivity,chaperone;Massion,MCP 0.0348 upHSP90AB1 candidatebiomarker,ATPaseactivity,chaperone;Massion,MCP 0.0196 upIDH1 Carbohydratemetabolism;Massion,MCP 0.0106 upIDH2 Carbohydratemetabolism;Massion,MCP 0.0348 upIGF2BP2 HepatocellularCarcinomaAutoantigenP62 0.0455 upLDHB Carbohydratemetabolism;Massion,MCP 0.0196 upLGALS7B hypopharynxcarcinoma,laryngealsquamouscellcarcinoma 0.0196 upME2 Carbohydratemetabolism;Massion,MCP 0.0196 upMLF1 p53regulator,Transcriptionfactor 0.0348 downMVP Massion,MCP 0.0348 upPFKL Carbohydratemetabolism 0.0455 upPFKP Carbohydratemetabolism;Massion,MCP 0.0196 upPGD Carbohydratemetabolism;Massion,MCP 0.0196 upPGK1 Carbohydratemetabolism;Massion,MCP 0.0196 upPGM1 Carbohydratemetabolism 0.0196 upPKM2 Carbohydratemetabolism 0.0027 upPYGB Carbohydratemetabolism;Massion,MCP 0.0263 upRAD23B DNArepairfunction 0.0077 upS100A2 Undetectedincontrol,Tumorsuppressor;Massion,MCP 0.0348 upSERPINB1 Massion,MCP 0.0348 upSFN Undetectedincontrol,lungnodulemetastasis;Massion,MCP;Spira,PNAS 0.0077 upUBA1 Massion,MCP 0.0348 upYWHAH Massion,MCP 0.0106 upTrendp>0.05

G6PD glucose-6-phosphatedehydrogenase 0.1824 upGAPDH glyceraldehyde-3-phosphatedehydrogenase 0.5785 downGLUD1 glutamatedehydrogenase1 0.2216 upGLUD2 glutamatedehydrogenase2 2n/a 2n/aGLUT1/SLC2A1 solutecarrierfamily2(facilitatedglucosetransporter),member1 0.0589 upLDHA lactatedehydrogenaseA 0.7389 downTALDO1 transaldolase1 0.2216 upTKT transketolase 0.0956 up1MassionMCP(MolCellProt.2014),CrystallBMC(BMCGenomics2012),SpiraPNAS(Proc.Natl.Acad.Sci.2004)2Notidentifiedbyshotgunanalysis

SupplementalTableS7:PeptidesequencesusedforParallelReactionMonitoringMassSpectrometry Protein Peptide Protein Peptide Protein Peptide Protein Peptide1 ACSF3 LPGSVGTPLPGVQVR 11 FASN LQVVDQPLPVR 21 IDH2 YFDLGLPNR 34 PKM2 LDIDSPPITAR ACSF3 SAFTLDGWFK FASN VLFPATGYLSIVWK IDH2 ATDFVADR PKM2 IYVDDGLISLQVK

FASN LPEDPLLSGLLDSPALK IDH2 TIEAEAAHGTVTR PKM2 EAEAAIYHLQLFEELR

2 ALDH1A1 VAFTGSTEVGK FASN FPQLDSTSFANSR

PKM2 LAPITSDPTEATAVGAVEASFK ALDH1A1 IFVEESIYDEFVR

22 IGF2BP2 ILVPTQFVGAIIGK PKM2 C[+57]C[+57]SGAIIVLTK

ALDH1A1 ILDLIESGK 12 G6PD GGYFDEFGIIR IGF2BP2 IAPAEGPDVSER ALDH1A1 ANNTFYGLSAGVFTK G6PD DGLLPENTFIVGYAR IGF2BP2 TVNELQNLTSAEVIVPR 35 PYGB GLAGLGDVAEVR

PYGB DYFFALAHTVR3 ALDH3A1 FDHILYTGSTGVGK 13 GAPDH VLAAVYK 23 LDHA LVIITAGAR PYGB DFYELEPEK ALDH3A1 VAYGGTGDAATR GAPDH ELSDIAHR

PYGB LLPLVSDEVFIR

ALDH3A1 SLEEAIQFINQR GAPDH LQSIGTENTEENR 24 LDHB FIIPQIVK PYGB VEDVEALDR ALDH3A1 SFETFSHR GAPDH GILAADESTGSIAK LDHB SADTLWDIQK

GAPDH GALQNIIPASTGAAK

36 RAD23B IDIDPEETVK4 ALOX15 TVGEDPQGLFQK GAPDH VGVNGFGR 25 LGALS7B LDTSEVVFNSK RAD23B ASFNNPDR ALOX15 LYDLPVDER GAPDH LVINGNPITIFQER LGALS7B GQPFEVLIIASDDGFK

ALOX15 VDFEVSLAK

LGALS7B AVVGDAQYHHFR 37 S100A2 ELPSFVGEK ALOX15 SSFYAQDALR 14 GBL1 AYVAVDGIPQGVLER LGALS7B AVVGDAQYHHFR

GLB1 TEAVASSLYDILAR

38 SERPINB1 FAYGYIEDLK5 ANXA2 AAYTNFDAER GLB1 VNYGAYINDFK 26 ME2 IETQDIQALR SERPINB1 IEEQLTLEK ANXA2 DALNIETAIK

ME2 HISDSVFLEAAK SERPINB1 LEESYTLNSDLAR

ANXA2 TPAQYDASELK 15 GLUD1 NYTDNELEK

ANXA2 TNQELQEINR GLUD1 HGGTIPIVPTAEFQDR27 MLF1 SFSEPFGR 39 SFN LGVQDLFNSSK

MLF1 DLLSISDGR SFN VLSSIEQK6 ANXA3 DYPDFSPSVDAEAIQK 16 GLUD2 YSTDVSVDEVK MLF1 VFQASTQTR SFN YLAEVATGDDK ANXA3 GAGTNEDALIEILTTR GLUD2 YNLGLDLR

ANXA3 SLGDDISSETSGDFR GLUD2 TAAYVNAIEK 28 MVP GPLEYVPSAK 40 TALDO1 VSTEVDAR ANXA3 GIGTDEFTLNR

MVP TAVFGFETSEAK TALDO1 SYEPLEDPGVK

ANXA3 SEIDLLDIR 17 GLUT1 VTILELFR MVP IEGEGSVLQAK TALDO1 LFVLFGAEILK

GLUT1 TFDEIASGFR

TALDO1 LSSTWEGIQAGK

7 ANXA6 DAFVAIVQSVK

29 PFKL SEWGSLLEELVAEGK ANXA6 SLHQAIEGDTSGDFLK 18 HSP90AA1APFDLFENR PFKL TFVLEVMGR 41 TKT DAIAQAVR

ANXA6 SLHQAIEGDTSGDFLK HSP90AA1LGIHEDSQNR PFKL VTVLGHVQR TKT AVELAANTK ANXZ6 LVFDEYLK HSP90AA1DQVANSAFVER

TKT IIALDGDTK

30 PFKP ELVVTQLGYDTR 8 CEACAM5 SDLVNEEATGQFR 19 HSP90AB1NPDDITQEEYGEFYK

42 UBA1 ALPAVQQNNLDEDLIR

HSP90AB1LGIHEDSTNR 31 PGD VDDFLANEAK UBA1 YDGQVAVFGSDLQEK9 DLST TPAFAESVTEGDVR HSP90AB1DIFQEIYDK PGD SFLEDIR UBA1 LAGTQPLEVLEAVQR DLST VEGGTPLFTLR HSP90AB1TVEAEAAHGTVTR

UBA1 AENYDIPSADR

DLST LGFMSAFVK

32 PGK1 YSLEPVAVELK

20 IDH1 HAYGDQYR PGK1 AC[+57]ANPAAGSVILLENLR 43 YWHAH AVTELNEPLSNEDR

10 EML4 VQQQEDEITVLK IDH1 VEITYTPSDGTQK

YWHAH YLAEVASGEK EML4 LSLPQNETVADTTLTK

33 PGM1 VDLGVLGK YWHAH NSVVEASEAAYK

PGM1 LSGTGSAGATIR

SupplementalTableS8.ValidationofoverexpressedcarbohydratemetabolicenzymesbyParallelReactionMonitoringMassSpectrometry

Gene Proteinname Pathway ICC pvalue GLB1 galactosidase,beta1 Galactosemetabolism 0.000 0.018 * PYGB phosphorylase,glycogen;brain Glycogenolysis 0.608 0.019 PGM1 phosphoglucomutase1 Glucosemetabolism 0.732 0.024 PGD phosphogluconatedehydrogenase Pentosephosphatepathway 0.534 0.008 * PFKL phosphofructokinase,liver Glycolysis 0.906 0.140 * PFKP phosphofructokinase,platelet Glycolysis 0.670 0.025 PGK1 phosphoglyceratekinase1 Glycolysis 0.901 0.085 * PKM2 pyruvatekinase,muscle Glycolysis 0.493 0.111 LDHB lactatedehydrogenaseB Glycolysis 0.898 0.166 IDH1 isocitratedehydrogenase1(NADP+),soluble TCAcycle 0.980 0.062 IDH2 isocitratedehydrogenase2(NADP+),mitochondrial TCAcycle 0.953 0.100 DLST dihydrolipoamideS-succinyltransferase TCAcycle 0.208 0.049 ME2 malicenzyme2,NAD(+)-dependent,mitochondrial TCAcycle 0.965 0.170 *ratelimitingenzyme

SupplementalTableS9:ExpressionofselectedgenesintheRNAseqdataset.Metabolicenzymesareinboldfonts.Gene Genename Adjustedpvalue GLB1 Galactosidase,beta1 0.0107 ALDH1A1 Aldehydedehydrogenase1family,memberA1 0.0447 PYGB Phosphorylase,glycogen;brain 0.0784 LDHB LactatedehydrogenaseB 0.0952 IDH2 Isocitratedehydrogenase2(NADP+),mitochondrial 0.1206 ANXA2 AnnexinA2 0.1328 PGK1 Phosphoglyceratekinase1 0.1661 UBA1 Ubiquitin-likemodifieractivatingenzyme1 0.1795 UGP2 UDP-glucosepyrophosphorylase2 0.2080 ALOX15 Arachidonate15-lipoxygenase 0.2373 ME2 Malicenzyme2,NAD(+)-dependent,mitochondrial 0.2892 PGD Phosphogluconatedehydrogenase 0.2979 BRCA2 Breastcancer2,earlyonset 0.2982 CAPS Calcyphosine 0.2988 ANXA6 AnnexinA6 0.3009 PFKP Phosphofructokinase,platelet 0.3749 HSP90AB1 Heatshockprotein90kDaalpha(cytosolic),classBmember1 0.4651 HSP90AA1 Heatshockprotein90kDaalpha(cytosolic),classAmember1 0.4705 BCAS1 Breastcarcinomaamplifiedsequence1 0.5136 CEACAM5 Carcinoembryonicantigen-relatedcelladhesionmolecule5 0.5591 ALDH3A1 Aldehydedehydrogenase3family,memberA1 0.5715 FASN Fattyacidsynthase 0.5833 RAD23B RAD23homologB(S.cerevisiae) 0.5882 SFTPB SurfactantproteinB 0.6392 PKM2 Pyruvatekinase,muscle 0.6677 SERPINB1 Serpinpeptidaseinhibitor,cladeB(ovalbumin),member1 0.6757 PFKL Phosphofructokinase,liver 0.6782 PGM1 Phosphoglucomutase1 0.7029 SFN Stratifin 0.7152 S100A2 S100calciumbindingproteinA2 0.7309 MLF1 Myeloidleukemiafactor1 0.7970 YWHAH Tyrosine3-monooxygenase/tryptophan5-monooxygenaseactivationprotein,eta

polypeptide 0.8104

CYP1B1 CytochromeP450,family1,subfamilyB,polypeptide1 0.8320 IDH1 Isocitratedehydrogenase1(NADP+),soluble 0.9211 ANXA3 AnnexinA3 0.9360 LGALS7B Lectin,galactoside-binding,soluble,7B 0.9406 MVP Majorvaultprotein 0.9628 DLG5 Discs,largehomolog5(Drosophila) 0.9704 IGF2BP2 Insulin-likegrowthfactor2mRNAbindingprotein2 0.9920 DLST DihydrolipoamideS-succinyltransferase(E2componentof2-oxo-glutaratecomplex) 0.9993 EML2 Echinodermmicrotubuleassociatedproteinlike2 notdetected EML4 Echinodermmicrotubuleassociatedproteinlike4 notdetected AKR1B10 Aldo-ketoreductasefamily1,memberB10(aldosereductase) notdetected ACSF3 Acyl-CoAsynthetasefamilymember3 notdetected SHROOM3 Shroomfamilymember3 notdetected