Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

Fredolini, Claudia; Pathak, Khyatiben V.; Paris, Luisa; Chapple, Kristina M.; Tsantilas, Kristine A.; Rosenow, Matthew; Tegeler, Tony J.; Garcia-Mansfield, Krystine; Tamburro, Davide; Zhou, Weidong; Russo, Paul; Massarut, Samuele; Facchiano, Francesco; Belluco, Claudio; De Maria, Ruggero; Garaci, Enrico; Liotta, Lance; Petricoin, Emanuel F.; Pirrotte, Patrick

doi:10.1186/s13058-020-01373-9

Table 2 Breast cancer candidate serum biomarkers

From: Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

#	Accession number	Uniprot ID	Gene	Description	MW (kDa)	Abundance (ppm)	GO-CC	Diff (%)	Cases (%)	Breast-specific	Novel
1	124248516	P59665	DEFA1	Alpha-defensin 1	10	138		63	53
2	4759070	Q16627	CCL14	Chemokine (C-C motif) ligand 14 isoform 1 precursor	11	83	ES	164	32
3	4507065	P03973	SLPI	Secretory leukocyte peptidase inhibitor precursor	14	9.52	EM	50	21	SPECIFIC
4	4826898	P07737	PFN1	Profilin 1	15	207	EE	108	63	SPECIFIC
5	5031635	P23528	CFL1	Cofilin 1 (non-muscle)	19	115	EM	133	58
6	33946278	Q9Y281	CFL2	Cofilin 2	19	21.3	ES	80	37
7	34850061	P62834	RAP1A	RAP1A, member of RAS oncogene family*	21	0.35	M	100	26	SPECIFIC
8	4885375	P16403	HIST1H1C	Histone cluster 1, H1c	21	6.45	N	59	21	SPECIFIC
9	4506413	P61224	RAP1B	RAP1B, member of RAS oncogene family-like	21	0.67	M	167	74	SPECIFIC
10	148227764	Q93045	STMN2	Superiorcervical ganglia, neural specific 10	21	1.59	EE	120	53	SPECIFIC
11	33695095	P13224	GP1BB	Glycoprotein Ib, beta polypeptide precursor	22	0.13	EE	133	21
12	4504073	P61026	RAB10	Ras-related GTP-binding protein RAB10	22	0.11	M	145	58	SPECIFIC
13	4507513	P35625	TIMP3	Tissue inhibitor of metalloproteinase 3 precursor	24	N/A	EM	53	47		NOVEL
14	4507651	P67936	TPM4	Tropomyosin 4 isoform 2	29	125	M	173	21	SPECIFIC
15	24234708	Q99697	PITX2	Paired-like homeodomain transcription factor 2 isoform b	35	N/A	N	50	26		NOVEL
16	37550464	A6NMN3	FAM170B	PREDICTED:family with sequence similarity 170,member B	36	3.16	M	67	21
17	209862875	Q7Z4I7	LIMS2	LIM and senescent cell antigen-like domains 2 isoform 1	38	0.43	M	200	21	SPECIFIC
18	156523970	P02765	AHSG	Alpha-2-HS-glycoprotein	39	8613	ES	50	63	SPECIFIC
19	156616273	P08567	PLEK	Pleckstrin	40	49.4	ES	143	32
20	4501889	P63267	ACTG2	Actin, gamma 2 propeptide	42	25.6	ES	114	100
21	20127528	P63261	ACTG1	Actin, gamma 1 propeptide	42	0.78	M	120	32
22	4501887	Q9HBI1	PARVB	Parvin, beta isoform b	42	147	EM	112	100	SPECIFIC
23	39725934	P36955	SERPINF1	Serine (or cysteine) proteinase inhibitor, clade F	46	3589	EM	111	21
24	9966913	Q9P1U1	ACTR3B	Actin-related protein 3-beta isoform 1	48	0.08	EE	200	26	SPECIFIC
25	55770868	I0CMK4	TUBB4Q	Tubulin, beta polypeptide 4, member Q	48	0.32		164	26
26	17921989	Q6PEY2	TUBA3E	Tubulin, alpha 3e	50	3.5	EE	94	47	SPECIFIC
27	46409270	Q9H4B7	TUBB1	Beta tubulin 1, class VI	50	1.63	N	98	63	SPECIFIC
28	4507729	Q9BQE3	TUBA1C	Tubulin alpha 6	50	2.03	EE	57	21	SPECIFIC
29	14210536	P68366	TUBA4A	Tubulin, alpha 4a	50	0.53	N	89	37	SPECIFIC
30	14389309	Q13885	TUBB2A	Tubulin, beta 2	50	2.33	Mi	92	89	SPECIFIC
31	13562114	Q9BUF5	TUBB6	Tubulin, beta 6	50	2.56	EE	72	68	SPECIFIC
32	4503649	P00740	F9	Coagulation factor IX preproprotein	52	685	ES	200	21
33	32483410	P38435	GC	Vitamin D-binding protein precursor	53	4435	M	200	26	SPECIFIC
34	21071030	Q9Y243	AKT3	AKT3 kinase isoform 2	54	8804	ES	150	32	SPECIFIC
35	32307163	P04217	A1BG	Alpha 1B-glycoprotein precursor	54	N/A	M	57	42
36	148746204	Q9Y251	HPSE	Heparanase	61	0.02	ER	156	63
37	13540563	Q9BXR6	CFHR5	Complement factor H-related 5	64	62.4	ER	67	26
38	4504383	Q04756	HGFAC	HGF activator preproprotein	71	534	ES	76	79
39	41281905	Q86UX7	FERMT3	Fermitin family homolog 3 long form	76	4.34	ER	123	89	SPECIFIC
40	54607120	P02788	LTF	Lactotransferrin precursor	78	45.4	ES	51	63
41	205277383	P26927	MST1	Macrophage stimulating 1 (hepatocyte growth factor-like)	82	269	ES	111	21	SPECIFIC
42	119395709	P00488	F13A1	Coagulation factor XIII A1 subunit precursor	83	37.7	ER	63	21	SPECIFIC
43	4504165	P06396	GSN	Gelsolin isoform a precursor	86	8905	ES	120	21	SPECIFIC
44	47078292	P05106	ITGB3	Integrin beta chain, beta 3 precursor	87	1.46	EE	160	63	SPECIFIC
45	4501891	P12814	ACTN1	Actinin, alpha 1 isoform b	103	6.5	ES	160	58
46	5453579	P13497	BMP1	Bone morphogenetic protein 1 isoform 3 precursor	111	1.38	EM	133	26	SPECIFIC
47	88758615	P08514	ITGA2B	Integrin alpha 2b preproprotein *	113	3.1	M	144	100	SPECIFIC
48	7669550	P18206	VCL	Vinculin isoform meta-VCL	124	94.5	M	153	21
49	40317626	P07996	THBS1	Thrombospondin 1 precursor	129	41.4	EM	94	100	SPECIFIC
50	12667788	P35579	MYH9	Myosin, heavy polypeptide 9, non-muscle	227	2.67	EM	200	21	SPECIFIC
51	223029410	Q9Y490	TLN1	Talin 1 *	270	22.5	ER	131	89	SPECIFIC
52	156938343	Q9Y4G6	TLN2	Talin 2	272	0.32	M	114	42	SPECIFIC
53	105990514	O75369	FLNB	Filamin B, beta (actin binding protein 278)	278	0.24	EM	86	32
54	116063573	P21333	FLNA	Filamin A, alpha isoform 1 *	280	9.63	EM	154	89	SPECIFIC
55	15147337	O95071	UBR5	Ubiquitin protein ligase E3 component n-recognin 5	309	0.03	M	59	42
56	33350932	Q14204	DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	532	0.04	EM	67	21	SPECIFIC

Abundance (ppm): protein abundance in plasma according to the PaxDB integrated plasma database. GO-CC Gene Ontology category cellular component, ES extracellular space, ER extracellular region, EM extracellular matrix, EE extracellular exosomes, M membrane, N nucleus, C cytoskeleton, Diff (%) relative difference in abundance (percentage) between cases and controls, Cases (%) percentage of breast cancer cases in which the protein is present, Breast-specific increased abundance in breast cancer patients sera only, Novel not yet reported in PaxDB (plasma, mass spectrometry)

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ISSN: 1465-542X

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