Table III. List of the proteins analyzed by SRM/MRM and their quantitation data using iTRAQ. p values were calculated by t-test. TM, number of transmembrane domain. C/P, average ratio of cancer without metastasis to polyps. Cm/C, average ratio of cancer with metastasis to cancer without metastasis. Cm/P, average ratio of cancer with metastasis to polyps.

A. The list of proteins increased in expression between polyps and cancer without metastasis (n = 66)
Accession	Protein name	Gene name	TM	GO (mem)	GO (extra)	C/P	p value	Cm/C	p value	Cm/P	p value
Q12884	Seprase	FAP	1	mem		5.98	<0.01	0.67	0.190	4.03	0.029
P32926	Desmoglein-3	DSG3	0	mem		4.54	<0.01	0.41	0.083	1.87	0.323
Q6P5W5	Zinc transporter ZIP4	SLC39A4	7	mem		4.35	0.075	0.42	0.189	1.84	0.217
Q8NFJ5	Retinoic acid-induced protein 3	GPRC5A	7	mem		3.99	<0.01	0.77	0.359	3.06	0.012
P40199	Carcinoembryonic antigen-related cell adhesion molecule 6	CEACAM6	0	mem		3.69	0.029	0.85	0.690	3.12	0.031
O95832	Claudin-1	CLDN1	4	mem		3.47	0.054	0.51	0.180	1.77	0.127
Q8TF66	Leucine-rich repeat-containing protein 15	LRRC15	1	mem		3.40	0.032	0.58	0.193	1.96	0.060
P24158	Myeloblastin	PRTN3	0	mem	extra	3.35	0.098	0.38	0.134	1.28	0.526
P50150	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4	GNG4	0	mem		3.31	0.074	0.77	0.570	2.56	0.051
P80511	Protein S100-A12	S100A12	0	mem	extra	3.28	0.068	1.06	0.857	3.46	0.070
P06731	Carcinoembryonic antigen-related cell adhesion molecule 5	CEACAM5	0	mem		3.27	<0.01	0.79	0.275	2.57	<0.01
Q9UKX5	Integrin alpha-11	ITGA11	1	mem		3.23	<0.01	0.62	0.081	2.00	0.016
Q10588	ADP-ribosyl cyclase 2	BST1	1	mem		3.16	0.023	0.55	0.102	1.75	0.033
P08253	72 kDa type IV collagenase	MMP2	0	mem	extra	3.02	<0.01	0.39	<0.01	1.19	0.599
Q9H6X2	Anthrax toxin receptor 1	ANTXR1	1	mem		2.98	<0.01	0.70	0.027	2.09	<0.01
Q9Y6I8	Peroxisomal membrane protein 4	PXMP4	0	mem		2.97	<0.01	0.74	0.084	2.19	<0.01
Q12805	EGF-containing fibulin-like extracellular matrix protein 1	EFEMP1	0	mem	extra	2.97	<0.01	0.57	0.037	1.71	0.040
Q14767	Latent-transforming growth factor beta-binding protein 2	LTBP2	0	mem	extra	2.91	<0.01	0.69	0.182	2.01	0.141
P16444	Dipeptidase 1	DPEP1	0	mem		2.85	0.033	1.06	0.854	3.02	<0.01
P84157	Matrix-remodeling-associated protein 7	MXRA7	1	mem		2.82	0.069	0.45	0.112	1.26	0.569
P11169	Solute carrier family 2, facilitated glucose transporter member 3	SLC2A3	10	mem		2.74	0.051	0.58	0.181	1.60	0.064
P08648	Integrin alpha-5	ITGA5	1	mem		2.59	<0.01	0.66	0.056	1.70	0.044
P55001	Microfibrillar-associated protein 2	MFAP2	0		extra	2.56	<0.01	0.46	<0.01	1.16	0.322
Q9ULK5	Vang-like protein 2	VANGL2	4	mem		2.55	0.098	0.39	0.086	1.00	0.989
Q5BJF2	Transmembrane protein 97	TMEM97	4	mem		2.54	<0.01	0.73	0.250	1.85	0.040
Q07075	Glutamyl aminopeptidase	ENPEP	1	mem		2.53	<0.01	0.70	0.201	1.77	0.104
Q9UGT4	Sushi domain-containing protein 2	SUSD2	1	mem		2.46	0.013	0.58	0.066	1.43	0.062
Q8N6Q3	CD177 antigen	CD177	0	mem		2.45	0.031	0.50	0.055	1.23	0.378
P07093	Glia-derived nexin	SERPINE2	0	mem	extra	2.43	0.059	0.85	0.699	2.06	0.132
Q96KR6	Transmembrane protein C20orf108	C20orf108	3	mem		2.39	0.020	0.73	0.287	1.75	0.041
P09619	Beta-type platelet-derived growth factor receptor	PDGFRB	1	mem		2.38	<0.01	0.85	0.423	2.01	0.014
Q7L4E1	Protein FAM73B	FAM73B	0	mem		2.34	<0.01	0.50	<0.01	1.17	0.289
O75954	Tetraspanin-9	TSPAN9	4	mem		2.31	<0.01	0.70	0.088	1.61	<0.01
Q9Y625	Glypican-6	GPC6	0	mem	extra	2.31	<0.01	0.63	0.055	1.45	0.179
Q8IUS5	Epoxide hydrolase 4	EPHX4	1	mem		2.29	0.043	1.13	0.614	2.59	<0.01
P36269	Gamma-glutamyltransferase 5	GGT5	1	mem		2.28	<0.01	0.71	0.172	1.63	0.047
Q8IWU6	Extracellular sulfatase Sulf-1	SULF1	0		extra	2.28	<0.01	0.82	0.445	1.88	0.074
Q6ZMP0	Thrombospondin type-1 domain-containing protein 4	THSD4	0		extra	2.26	0.042	0.59	0.278	1.35	0.656
P21730	C5a anaphylatoxin chemotactic receptor	C5AR1	7	mem		2.22	0.090	0.42	0.065	0.93	0.776
P35555	Fibrillin-1	FBN1	0	mem	extra	2.22	0.039	0.38	0.022	0.84	0.363
P98095	Fibulin-2	FBLN2	0		extra	2.20	<0.01	0.68	0.206	1.49	0.300
P31997	Carcinoembryonic antigen-related cell adhesion molecule 8	CEACAM8	0	mem	extra	2.20	0.090	0.51	0.118	1.11	0.592
Q14766	Latent-transforming growth factor beta-binding protein 1	LTBP1	0	mem	extra	2.19	<0.01	0.62	0.015	1.35	0.087
Q99720	Sigma non-opioid intracellular receptor 1	SIGMAR1	1	mem		2.19	<0.01	0.86	0.439	1.88	<0.01
P50281	Matrix metalloproteinase-14	MMP14	1	mem	extra	2.19	<0.01	0.70	0.096	1.53	0.078
P02786	Transferrin receptor protein 1	TFRC	1	mem	extra	2.18	<0.01	1.09	0.579	2.38	<0.01
P31431	Syndecan-4	SDC4	1	mem	extra	2.16	0.082	0.55	0.143	1.20	0.172
Q9UBG0	C-type mannose receptor 2	MRC2	1	mem		2.15	<0.01	0.68	0.078	1.47	0.230
Q9P121	Neurotrimin	NTM	0	mem		2.15	0.058	0.56	0.082	1.20	0.368
P09486	SPARC	SPARC	0		extra	2.14	<0.01	0.85	0.321	1.81	0.025
P05106	Integrin beta-3	ITGB3	1	mem		2.13	0.023	0.70	0.245	1.49	0.165
P04792	Heat shock protein beta-1	HSPB1	0	mem		2.11	<0.01	1.34	0.421	2.83	0.035
Q9NVM1	Protein FAM176B	FAM176B	1	mem		2.08	0.046	1.03	0.951	2.13	0.276
P08514	Integrin alpha-IIb	ITGA2B	1	mem		2.08	0.083	0.88	0.759	1.83	0.130
Q8WUY1	UPF0670 protein C8orf55	C8orf55	1		extra	2.07	<0.01	1.40	0.158	2.90	<0.01
P12314	High affinity immunoglobulin gamma Fc receptor I	FCGR1A	1	mem		2.07	<0.01	0.68	0.105	1.41	0.149
P04216	Thy-1 mem glycoprotein	THY1	0	mem		2.06	<0.01	0.77	0.092	1.59	0.023
P08174	Complement decay-accelerating factor	CD55	0	mem	extra	2.05	<0.01	1.04	0.879	2.13	0.020
Q96HV5	Transmembrane protein 41A	TMEM41A	6	mem		2.04	<0.01	0.76	0.060	1.54	<0.01
Q9ULS5	Transmembrane and coiled-coil domains protein 3	TMCC3	2	mem		2.04	0.040	0.61	0.195	1.25	0.434
Q01628	Interferon-induced transmembrane protein 3	IFITM3	2	mem		2.04	0.021	1.07	0.770	2.18	<0.01
P04920	Anion exchange protein 2	SLC4A2	11	mem		2.04	0.044	0.82	0.441	1.66	<0.01
Q9Y289	Sodium-dependent multivitamin transporter	SLC5A6	14	mem		2.03	<0.01	0.65	0.030	1.31	0.086
P30273	High affinity immunoglobulin epsilon receptor subunit gamma	FCER1G	1	mem		2.02	<0.01	0.71	0.140	1.43	0.141
P08473	Neprilysin	MME	1	mem		2.01	0.097	0.87	0.626	1.74	0.030
P13688	Carcinoembryonic antigen-related cell adhesion molecule 1	CEACAM1	1	mem	extra	2.00	0.014	0.74	0.169	1.48	0.173

B. The list of proteins increased in expression between cancer without and with metastasis (n = 10)
Accession	Protein name	Gene name	TM	GO (mem)	GO (extra)	C/P	p value	Cm/C	p value	Cm/P	p value
Q96HR9	Receptor expression-enhancing protein 6	REEP6	2	mem		1.13	0.651	3.18	0.070	3.61	0.035
P05451	Lithostathine-1-alpha	REG1A	0		extra	0.20	0.164	3.08	<0.01	0.60	0.379
Q8N323	Protein FAM55A	FAM55A	1		extra	0.22	0.102	2.98	0.057	0.65	0.416
O95395	Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3	GCNT3	1	mem		0.82	0.595	2.85	0.086	2.33	0.089
O95994	Anterior gradient protein 2 homolog	AGR2	0		extra	0.44	0.012	2.56	0.094	1.12	0.727
Q9NRD8	Dual oxidase 2	DUOX2	6	mem		0.43	0.081	2.51	0.045	1.07	0.843
Q8TD06	Anterior gradient protein 3 homolog	AGR3	0		extra	0.51	0.028	2.49	0.017	1.26	0.301
Q09327	Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase	MGAT3	1	mem		0.89	0.694	2.24	0.046	1.99	0.024
Q9Y5L3	Ectonucleoside triphosphate diphosphohydrolase 2	ENTPD2	2	mem	extra	1.36	0.369	2.09	0.028	2.83	<0.01
Q8NCC5	Sugar phosphate exchanger 3	SLC37A3	12	mem		0.94	0.838	2.06	0.016	1.92	0.030

C. The list of proteins decreased in expression between polyps and cancer without metastasis (n = 13)
Accession	Protein name	Gene name	TM	GO (mem)	GO (extra)	C/P	p Value	Cm/C	p Value	Cm/P	p Value
A8K7I4	Calcium-activated chloride channel regulator 1	CLCA1	0	mem	extra	0.14	<0.01	0.85	0.673	0.12	<0.01
Q01524	Defensin-6	DEFA6	0		extra	0.18	0.053	0.69	0.428	0.12	0.043
Q9Y6R7	IgGFc-binding protein	FCGBP	0	mem	extra	0.23	<0.01	1.12	0.830	0.25	<0.01
Q6ZMB0	UDP-GlcNAc:betaGalbeta-1,3-N-acetylglucosaminyltransferase 6	B3GNT6	1	mem		0.26	<0.01	1.10	0.713	0.29	<0.01
Q02817	Mucin-2	MUC2	0		extra	0.26	<0.01	1.31	0.537	0.34	<0.01
Q07654	Trefoil factor 3	TFF3	0		extra	0.32	<0.01	1.14	0.651	0.37	<0.01
Q9HC84	Mucin-5B	MUC5B	0		extra	0.36	0.038	1.29	0.352	0.47	0.042
P27216	Annexin A13	ANXA13	0	mem		0.37	<0.01	1.24	0.574	0.46	0.018
P24588	A-kinase anchor protein 5	AKAP5	0	mem		0.43	0.017	1.12	0.606	0.48	0.011
Q7Z3J2	UPF0505 protein C16orf62	C16orf62	0	mem		0.46	<0.01	1.39	0.072	0.65	<0.01
P13727	Bone marrow proteoglycan	PRG2	0		extra	0.48	0.045	0.89	0.695	0.43	0.021
Q6UXG2	UPF0577 protein KIAA1324	KIAA1324	1	mem		0.49	0.051	1.25	0.390	0.61	0.085
Q9Y2J2	Band 4.1-like protein 3	EPB41L3	0	mem		0.49	0.062	1.35	0.086	0.66	0.167

D. The list of proteins decreased in expression between cancer without and cancer with metastasis (n = 6)
Accession	Protein name	Gene name	TM	GO (mem)	GO (extra)	C/P	p Value	Cm/C	p Value	Cm/P	p Value
P08123	Collagen alpha-2(I) chain	COL1A2	0	mem		1.87	0.086	0.34	0.010	0.63	0.213
O75015	Low affinity immunoglobulin gamma Fc region receptor III-B	FCGR3B	1	mem		2.14	0.236	0.34	0.057	0.73	0.673
P02452	Collagen alpha-1(I) chain	COL1A1	0	mem	extra	1.86	0.109	0.36	0.025	0.66	0.252
P02461	Collagen alpha-1(III) chain	COL3A1	0	mem		1.70	0.182	0.39	0.039	0.66	0.152
Q15063	Periostin	POSTN	0	mem		1.57	0.214	0.43	<0.01	0.67	0.406
O43934	UNC93-like protein MFSD11	MFSD11	10	mem		1.27	0.434	0.45	0.067	0.58	0.110

E. The list of proteins increased in expression between polyps and cancer with metastasis (n = 10)
Accession	Protein name	Gene name	TM	GO (mem)	GO (extra)	C/P	p Value	Cm/C	p Value	Cm/P	p Value
P21589	5′-nucleotidase	NT5E	2	mem		1.69	0.104	1.41	0.447	2.39	0.082
Q92968	Peroxisomal membrane protein PEX13	PEX13	0	mem		1.35	0.012	1.73	0.031	2.34	0.012
O43291	Kunitz-type protease inhibitor 2	SPINT2	1	mem	extra	1.63	<0.01	1.39	0.419	2.27	0.087
Q8N4S7	Progestin and adipoQ receptor family member 4	PAQR4	3	mem		1.82	<0.01	1.23	0.342	2.25	0.019
Q8NBM4	Ubiquitin-associated domain-containing protein 2	UBAC2	4	mem		1.95	<0.01	1.14	0.441	2.22	<0.01
Q96CP7	TLC domain-containing protein 1	TLCD1	5	mem		1.33	0.288	1.67	0.226	2.21	0.100
P05546	Heparin cofactor 2	SERPIND1	0		extra	2.15	0.124	0.99	0.978	2.13	0.024
P11166	Solute carrier family 2, facilitated glucose transporter member 1	SLC2A1	12	mem		1.92	<0.01	1.10	0.716	2.11	0.031
Q9BQD7	Protein FAM173A	FAM173A	1	mem		1.55	<0.01	1.36	0.236	2.11	0.050
Q96B21	Transmembrane protein 45B	TMEM45B	5	mem		1.29	0.132	1.61	0.100	2.07	0.018