Emerging blood-based biomarkers for detection of gastric cancer

Table 1 Proteomics-based biomarker models for detection of gastric cancer

Biomarkermodel	Approach used	Sample size and type(cancer/controls)	Diagnostic value1	Ref.
Five peaks - 3316, 6629, 3217, 3952, 6431 Da	MB-WCX, MALDI-TOF-MS	T: GC = 32/HC = 32	AUC = 0.86-0.99 for individual features (P < 0.001),	Yang et al[148], 2012
		V: GC = 30	Sn = 79.3%, Sp = 86.5%
		(GC I-II = 8)/HC = 30	Sn = 71.7% for early stage GC
1546 Da (SERPINA1)	MB-WCX, MALDI-TOF-MS; ELISA for validation	T: GC = 70/HC = 72	AUC (1546 Da) = 0.83 (P < 0.001), AUC (5335 Da) = 0.87 (P < 0.001) - calculated for training set; in validation set SERPINA1 concentration was significantly higher for GC patients than for all other controls (P < 0.001) and ENOSF1 concentration was significantly higher for GC patients than HC (P < 0.001)	Yang et al[34], 2015
5335 Da (ENOSF1)		V: GC = 36/HC = 36, BGD = 30, other cancers = 108
Fibrinogen α-chain, apolipo	HPLC, LC-MS/MS	T: GC = 65/HC = 30, BGD = 23	Sn = 90.9%, Sp = 90.6% (P = NA)	Liu W et al[37], 2012
		V: GC = 44/ HC = 30, BGD = 23
Six peaks at 2873, 3163, 4526, 5762, 6121 and 7778 m/z; For stage I three peaks at 2873, 6121 and 7778 m/z	Protein Chip SELDI-TOF-MS	GC = 169 (GCI = 27)/HC = 83	Sn = 93.5%, Sp = 91.6%	Li et al[26], 2012
			Accuracy for stage I - 88.9%, (P = NA)
EGFR, proApoA1, ApoA1, TTR, RANTES, VN, DD, IL-6, A2M, CRP, PAI1	xMAP (Luminex), ELISA	T: GC = 120/BGD = 101, HC = 19	AUC = 0.95, (P < 0.05)	Ahn et al[35], 2012
		V: GC = 95 (GC I-II = 75)/BGD = 43, HC = 8	Sn = 88.8%, Sp = 89.7%
			Sn (I-II ) = 92.3%
			Sn (tumor size ≤ 2 cm) = 81.8%
Four peaks at 1867 (tubulin beta chain), 2701 (thymosin beta4 like protein3), 2094 (cytochrom b-c1 subunit), 1467 Da	MB-WCX, MALDI-TOF-MS	T: GC = 40/HC = 39	AUC (1867 Da) = 1,	Fan et al[30], 2013
		V: GC = 40/GA = 30, HC = 39	AUC (1467 Da) = 0.83
			AUC (2701 Da) = 0.71
			AUC (2094 Da) = 0.70 (P < 0.05)
			Sn = 95.0%, Sp = 97.1%
50 decision trees, 28 masses	Protein Chip SELDI-TOF-MS,	T: GC = 41/HC = 49	Sn = 100%, Sp = 96.7%	Ebert et al[24], 2004
		V: GC = 28; GCI = 9/HC = 30	For stage I Sn = 89.9%
			(P = NA )
Three peaks at 3946, 3503 and 15958 Da			Sn = 92.8%, Sp = 86.7%
			For stage I Sn = 89.9%
			(P = NA )

¹Diagnostic values listed for validation set, if not otherwise stated. A2M: Alfa 2 macroglobulin; Apo: Apolipoprotein; AUC: Area under the curve; BGD: Benign gastric diseases; CRP: C reactive protein; DD: D-dimer; ENOSF1: Isoform 2 of mitochondrial enolase superfamily member 1; EGFR: Epidermal growth factor receptor; GA: Gastric adenoma; GC (I-IV): Gastric cancer (TNM stages); HC: Healthy control; HPLC: High performance liquid chromatography; IL-6: Interleukin 6; LC: Liquid chromatography; MALDI-TOF-MS: Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry; MB-WCX: Magnetic bead based weak cation-exchange chromatography; NA: Not available; PAI1: Plasminogen activator inhibitor 1; proApo: Proapolopoprotein; RANTES: Regulated upon activation, normally T-expressed and presumably secreted; SELDI-TOF-MS: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry; SERPINA1: Serpin peptidase inhibitor clade A (alpha-1 antiproteinase, antitrypsin), member 1; Sn: Sensitivity; Sp: Specificity; T: Training set; TTR: Transthyretrin; V: Validation set; VN: Vitronectin.