Figures S6-S10 Copy

Figure S6

A B ER Complement proteins activation- NADP+ related 0.04 metabolism proteins Glycolytic process Ribosomal 0 Intermediate subunits filament Cell migration PC2 (12%) -0.04 Cell adhesion/ extracellular matrix

-0.08 Carbohydrate -0.04 0 0.04 metabolism Mitochondrial PC1 (26%) proteins Protein cluster 1 Protein cluster 2 Protein cluster 3 Protein cluster 1 Protein cluster 2 Protein cluster 3

C D Metabolic Progenitor-like Proliferative Inflammatory Ethanol oxidation Signaling by retinoic acid 1.5 Mitochondrial Fatty Acid Beta-Oxidation 0.5 Detoxification of Reactive Oxygen Species -0.5 Relative Signaling by Retinoic Acid expression -1.5 ADH4 ALDH1A1 DLD ADH1A RDH16 CPT1A Interleukin-12 signaling E Translation Pentose phosphate pathway

Paradoxical activation of RAF 0.5 signaling by kinase inactive BRAF 0.0 Activation of NF-kappaB in B cells Relative -0.5 expression Regulation of RAS by GAPs -1.0 EIF2S3 SRP14 EIF3A EEF2 EIF3H EEF1G Translation F Pentose phosphate pathway TNFR2 non-canonical NF-kB pathway 1.5 1.0 G2/M Transition 0.5 Adaptive Immune System 0.0 Relative

expression -0.5 Signaling by WNT G TALDO1 PGD G6PD PGM2 TKT Complement cascade Adaptive immune response 0 5 10 15 55 -log (p-value) 2.0 Protein cluster 1 Protein cluster 2 Protein cluster 3 1.0

Relative 0.0 expression -1.0 ITGB2 C3 CD14 ERAP1 VASP ITB1 Figure S7

A B Response to oxidative stress Fatty acid derivative metabolic process Carbohydrate metabolic process

Nucleobase metabolic process

m Cellular amino acid catabolic r

e process t

O Fatty acid beta-oxidation G

Mitochondrion organization

Terpenoid metabolic process

Malate metabolic process Organic hydroxy compound catabolic process 0 5 10 15 20 25 30 35 -log(p-value)

Carbohydrate Metabolic Process (GO:0005975, p = 7.51 × 10-12) C AGL AKR1A1 ALDH1A1 ALDH1B1 ALDH2 ALDH5A1 ALDOB CRYL1 CYB5A CYB5R3 DCXR FBP1 GAA GALM GAPDH GK GOT1 GOT2 GSTO1 IDH2 MDH1 MDH2 ME1 PC PCK1 PCK2 PGM1 PKLR PYGL RGN SLC25A1 SLC25A13 SNCA SORD TKFC UGP2 UGT2B7 Metabolic Progenitor-like Proliferative Inflammatory Response to Oxidative Stress (GO:0006979, p = 0.00236) D ACOX2 CAT CRAT CYCS ETFDH FABP1 GLYAT GPX1 MGST1 P4HB PARK7 PRDX1 PRDX3 PRDX6 SNCA SOD1 SOD2 TRAP1 Metabolic Progenitor-like Proliferative Inflammatory

Fatty Acid Beta-Oxidation (GO:0006635, p = 1.52 × 10-24) E ABCD3 ACAA1 ACAA2 ACADM ACADS ACADVL ACAT1 ACAT2 ACOX2 CPT1A CRAT DECR1 ECHDC2 ECHS1 ECI1 ECI2 EHHADH ETFA ETFDH HADH HADHA HADHB HSD17B4 IVD SCP2 Metabolic Progenitor-like Scale Proliferative 0.67 1 1.5 Inflammatory Figure S8

A B

Ribosomal subunit Chaperonin-containing T-complex Proteasome accessory complex Ribonucleoprotein granule

s Spliceosomal complex r m Nucleolus t e Regulation of protein localization to Cajal body Ribonucleoprotein complex biogenesis o n t l g y Posttranscriptional regulation of gene expression n e

G e tRNA aminoacylation for protein translation RNA localization Response to unfolded protein Regulation of endoribonuclease activity Cytoplasmic translation

0 5 10 15 20 25 30 35 40 45 -log(p-value)

Protein localization to Cajal body -7 -6 Ribonucleoprotein granule (p-value = 1.83 × 10 ) C (p-value = 1.12 × 10 ) D CKAP4 DDX1 DHX9 HNRNPL NCL PABPC1 PCBP1 PSMC2 RAC1 RPL28 RPL6 RPLP0 RPS4X RPS6 TUBB YBX1 CCT2 CCT3 CCT4 CCT5 CCT6A CCT7 CCT8 TCP1 Metabolic Metabolic Progenitor-like Progenitor-like Proliferative Proliferative Inflammatory Inflammatory

RNA splicing (p-value = 1.02 × 10-8) Regulation of ubiquitin protein ligase activity E F (p-value = 2.59 × 10-4) PSMC1 PSMC2 PSMD1 PSMD12 PSMD2 PSMD3 RPL11 RPL17 RPL23 RPL5 RPS7 SKP1 C1QBP DDX1 DDX39B DHX15 DHX9 HNRNPA1 HNRNPA2B1 HNRNPL HNRNPR HSPA1A HSPA8 KHSRP PABPC1 PCBP1 PCBP2 PPP2R1A PRDX5 PTBP1 RBMX RPS13 RTCB SF3A1 SF3B1 SFPQ SNRPD2 SYNCRIP U2AF2 YBX1 Metabolic Metabolic Progenitor-like Progenitor-like Proliferative Proliferative Inflammatory Inflammatory

Ribosomal subunit (p-value = 5.68 × 10-66) G RACK1 RPL10A RPL11 RPL12 RPL13 RPL14 RPL15 RPL17 RPL18 RPL18A RPL19 RPL23 RPL23A RPL24 RPL28 RPL3 RPL30 RPL34 RPL4 RPL5 RPL6 RPL7 RPL7A RPL8 RPL9 RPLP0 RPLP1 RPLP2 RPS10 RPS11 RPS12 RPS13 RPS14 RPS15A RPS16 RPS17 RPS19 RPS2 RPS20 RPS23 RPS25 RPS3 RPS3A RPS4X RPS5 RPS6 RPS7 RPS8 RPS9 RPSA Metabolic Progenitor-like Proliferative Inflammatory A Inflammatory Proliferative Progenitor-like Metabolic E C Inflammatory Proliferative Progenitor-like Metabolic Figure S9 GO term Po R s e i t i g v u e l

a re R t i o g H e M n u g y a

l a d u o Su c t l f ro a ro

i Ve Ex o c O t g p Ac n i e m

ACTR2 o e s ra rg l

t n l o ra o n i u t c

m a f i l

ANXA1 o v

e l c p a n c ACTR3 e f a o c e r e

i c t i l u b l ro n e c i l l o

l u l u u n I o a a c n n x l ALDOA d l a u m c a r a

i f d d l i o t r l c d r a ANXA4 a e p i e f o n m

m r Pro p

i i

APOA1 m g m ro c m f n a (GO:0032637, p-value=0.00726) m i

a e b e p f t m m t ro ri t t t a e n e l e a a e x r u u t

APOE t i i b m b o

n x

APOA2 n n n o o o En o o ry

Interleukin-8 production l re e e rg rg rg p m l o l i i

ro c c

ARPC1B d c re re re m a a a e

a o p p n n c n m s s o s l c ro ro i i e i i p p z p z z z d y b

ARPC2 BPI s o a o a a a e o c t c ra s o t n t t t n e n e l i i i i i i s n n o o n o o s s s s s i e n e n g n n g s e s e

ARPC4 s

ARPC5 CD14 0 Supramolecular fiberorganization(GO:0006956,p-value=4.01×10 CAPG CRP CAPZB 5 CD2AP LBP - l CDC42 o g 1 0

CFL1 PARK7 ( 1 p 0 - CLU v a l PYCARD u

COL12A1 e )

COL14A1 1

RAB1A 5 CORO1A CUL3 TMSB4X

EML2 2 0

EZR B D FLNA Inflammatory Proliferative Progenitor-like Metabolic FSCN1 GPX1 GSN HCLS1 HSPG2 KRT19 A2M KRT9 C1R C1S

LCP1 (GO:0006956, p-value=2.94 LUM C3 PARK7 C4BPA Complement activation PFN1 C5 PLS1 C6 -11 C7

PLS3 ) PYCARD C8A RDX C9 RHOA CFB S100A10 CFH SERPINH1 CFI

SNCA CLU × 10 TMSB4X F2 -6 TPM2 PROS1 ) TPM4 PSMA7 VASP SERPING1 ZYX VTN Figure S10 Gemcitabine FOLFIRINOX/FOLFOX Abraxane/Paclitaxel Tarceva/Erlotinib Radiation

p = 6.15 × 10-5 p = 0.031 p = 0.966 p = 0.120 p = 0.033 All samples

p = 0.758 p = 0.495 p = 0.008 p = 0.450 p = 0.338 Metabolic

p = 0.001 p = 0.067 p = 0.317 p = 0.097 p = 0.334 Progenitor-like Survival Probability

p = 0.180 p = 0.163 p = 0.585 p = 0.944 p = 0.192 Proliferative

p = 0.053 p = 0.364 p = 0.305 p = 0.413 p = 0.123 Inflammatory

Survival Days with the specified treatment without the specified treatment