Liquid biopsy of gastric cancer patients: Circulating tumor cells and cell-free nucleic acids

Table 1 Detection of circulating tumor cells in gastric cancer

Characteristic and number of patients		Control (n)	Detection method		Detection rate/statistic value		Ref.
Pre or post treatment	9 (PB)	4	RT-PCR	CEA mRNA	22.2%	(Pt.)	Funaki et al[133]
					0%	(Ctrl.)
I-IV	20 (PB)	22	RT-PCR	CEA mRNA	35%	(Pt.)	Mori et al[134]
					0%	(Ctrl.)
I-IV	49 (PB)	50	RT-PCR	CK19 mRNA	0%	(PB)	Aihara et al[135]
	21 (PV)				0%	(PV)
					0%	(Ctrl.)
I-IV	30 (PB)	58	RT-PCR	CK20 mRNA	16.7%	(Pt.)	Soeth et al[136]
					3.4%	(Ctrl.)
Inoperable/metastatic	34 (PB)	33	RT-PCR	CK19 mRNA	20.6%	(Pt.)	Yeh et al[137]
					0%	(Ctrl.)
I, III, IV	35 (PB)	9	RT-PCR	CEA mRNA	45.7%	(Pt.)	Noh et al[138]
					0%	(Ctrl.)
I-IV	52 (PB)	14	RT-PCR	CK19 mRNA	9.6%	(Pt.)	Majima et al[139]
					0%	(Ctrl.)
				CK20 mRNA	9.6%	(Pt.)
					1%	(Ctrl.)
I-IV	41 (PB)		RT-PCR	CEA mRNA	22.2%	(before curative surgery)	Nishida et al[60]
(36 with curative surgery)					33.3%	(during curative surgery)
(5 with inoperable)					80%	(inoperable Pt.)
I-IV	57 (PA)	30	RT-PCR	CEA mRNA	PA: 17.5%		Miyazono et al[59]
	49 (PV)				PV: 18.4%
	51 (SVC)				SVC: 21.6%
					8.8%	(before surgery)	At least either one positive in PA/PV/SVC
					33.3%	(during surgery)
					0%	(Ctrl.)
EGC, III	29 (PB)	15	RT-PCR	CEA mRNA	EGC: 22.2%	(after surgery)	Noh et al[140]
(paired, after surgery during surgery and follow-up)					IIIa: 20%
					IIIb: 26.7%
					Total: 24.1%
					EGC: 22.2%	(during follow-up)
					IIIa: 20%
					IIIb: 34.4%
					Total: 34.4%
					0%	(Ctrl.)
I-IV	106 (PB)		RT-PCR	CEA mRNA	40.6%		Sumikura et al[141]
(during surgery)
I-IV	41 (PB)	10	RT-PCR	CEA mRNA	24.4%	(Pt.)	Koike et al[142]
					0%	(Ctrl.)
I-IV	46 (PB) (18 EGJ caner)(28 with GC)	10 (with benign GI disease)100 (tumor-free Ctrl.)	qRT-PCROncoquick density gradient centrifugation	CK20 mRNA	27.8%	(Pt. with EGJ cancer)	Friederichs et al[143]
					21.4%	(Pt. with GC)
					0%	(with benign GI disease)
					1%	(tumor-free Ctrl.)
I-IV	59 (PB)	15	qRT-PCR	CEA mRNA	0%	(before surgery)	Ikeguchi et al[58]
					45.8%	(after surgery)
					0%	(Ctrl.)
I-IV	70 (PB)		RT-PCR	CK20 mRNA	36.6%	(Pt. with curative resection)	Illert et al[144]
(41 with curative resection)					44.8%	(Pt. with residual tumor)
(29 with residual tumor)					Total: 40%
I-III	46 (PB)	13	RT-PCR	CEA mRNA	52.2%	(before surgery)	Seo et al[145]
(with curative resection)					19.6%	(after surgery)
(paired, before and after surgery)					0%	(Ctrl.)
I-IV	52 (PB)	36	RT-PCR	c-Met mRNA	61.5%	(Pt.)	Uen et al[42]
					5.6%	(Ctrl.)
				MUC1 mRNA	71.2%	(Pt.)
					8.3%	(Ctrl.)
I-IV	42 (PB)	30	RT-PCR	hTERT mRNA	61.9%	(Pt.)	Wu et al[43]
					0%	(Ctrl.)
				CK19 mRNA	69.0%	(Pt.)
					3.3%	(Ctrl.)
				CK20 mRNA	61.9%	(Pt.)
					3.3%	(Ctrl.)
				CEA mRNA	78.6%	(Pt.)
					0%	(Ctrl.)
I-IV	64 (PB)	80	MAH	hTERT mRNA	81.3%		Wu et al[44]
				CK19 mRNA	78.1%
				CK20 mRNA	82.8%
				MUC1 mRNA	84.4%
					No detection in controls
I-IV	32 (PB)		FACS/ICC	CK8/18/19	21.9%	(before chemotherapy)	Kolodziejczyk et al[146]
(paired, before and after chemotherapy)					15.6%	(after chemotherapy)
I-IV	57 (PB)		FACS/ICC	CK8/18/19	54.4%	(before surgery)	Pituch-Noworolska et al[61]
	(before surgery)				21.2%	(after surgery)
	52 (PB)
	(after surgery)				26.8%	(TDB sample)
	56 (TDB)
I-IV	52 (PB)	20	qRT-PCR	CEA mRNA	5.0%	(before surgery)	Tani et al[147]
	(40 pre-ope)				16.7%	(after surgery)
	(12 post-ope)
I-IV	41 (PB)	41	Cell search system	EpCAM	14.3%	(Nonmetastatic GC)	Hiraiwa et al[55]
				CK8/18/19	55.6%	(metastatic GC)
					0%	(Ctrl.)
I-IV	101 (PB)	14	qRT-PCR	CK19 mRNA↑	P = 0.0127	Curative resection (n = 69) vs Ctrl. (n = 14)	Koga et al[148]
(69 with curative ope)					P = 0.0087	Non-curative resection (n = 32) vs Ctrl. (n = 14)
(32 with non-curative ope)				CK20 mRNA↑	P = 0.0022	Non-curative resection (n = 32) vs Ctrl. (n = 14)
I-IV	810 (PB)	29	RT-PCR	MT1-MMP mRNA	22.8%		Mimori et al[57]
					No data for Ctrl.
I-IV	55 (PB)	86	RT-PCR ELISA	Survivin mRNA↑	45.5%	(Pt.)	Yie et al[149]
					AUC = 0.772	Pt. (n = 55) vs Ctrl. (n = 86)
I-IV	70 (PB)	20	qRT-PCR	CEA mRNA	45.7%		Bertazza et al[150]
				CK19 mRNA	97.1%
				VEGF mRNA	38.6%
				Survivin mRNA	98.6%
					(Control samples were used the calibrator source)
I-IV	846 (PB)	25	qRT-PCR	uPAR mRNA↑	404/846 47.8%		Kita et al[151]
					P < 0.0001	Pt. (n = 846) vs Ctrl. (n = 25)
Advanced	52 (PB)		Cell search system	EpCAM	32.7%	(baseline)	Matsusaka et al[56]
(paired, before and during chemotherapy)				CK8/18/19	13.7%	(2 wk after chemotherapy)
					18.8%	(4 wk after chemotherapy)
I-IV	123 (PB)	30	qRT-PCR	CEA mRNA	36.6%	(Pt.)	Qiu et al[152]
					30%	(Ctrl.)
I-IV	30 (PB)		qRT-PCR	CK18 mRNA	I/II: 81.8%		Saad et al[153]
(after curative surgery)					III/IV: 31.6%
					Total: 50%
N/A	90 (PB)			miR-106a↑	P = 0.006	Pre-ope vs Ctrl.	Zhou et al[48]
(90 before surgery)					AUC = 0.684
(41 preoperative)					P = 0.016	Post-ope vs Ctrl.
(49 postoperative)				miR-17↑	P = 0.001	Pre-ope vs Ctrl.
					AUC = 0.743
					P = 0.019	Post-ope vs Ctrl.
I-IV	95 (PB)	21	qRT-PCR	B7-H3 mRNA↑	50.5%		Arigami et al[154]
					P < 0.0001	Pt. (n = 95) vs Ctrl. (n = 21)
					AUC = 0.86
I-IV	98 (PB)	30	RT-PCR ELISA	Survivin mRNA	I/II: 25%		Cao et al[155]
					III/IV: 56.1%
					I-IV: 45.9%
I-IV	93 (PB)	32	qRT-PCR	piR-651↓	P < 0.001	Pt. (n = 93) vs Ctrl. (n = 32)	Cui et al[49]
	(42 preo-ope)				AUC = 0.841
	(51 post-ope)			piR-823↓	P < 0.001
					AUC = 0.822
II-IV	35 (PB)	50	qRT-PCR	CEA mRNA	22.9%	(Pt.)	Dardaei et al[156]
				CK20 mRNA	37.1%	(Pt.)
				TFF1 mRNA	31.4%	(Pt.)
				MUC2 mRNA	22.9%	(Pt.)
					No detection in controls
I-IV	53 (PB)	20	qRT-PCR	miR-21↑	P < 0.0001	Pt. (n = 53) vs Ctrl. (n = 20)	Zheng et al[50]
					AUC = 0.853
I-IV	52 (PB)	15	qRT-PCR	miR-200c↑	P = 0.018	Pt. (n = 52) vs Ctrl. (n = 15)	Valladares-Ayerbes et al[51]
					AUC = 0.715
I-IV	40 (PB)	17	qRT-PCR	miR-421↑	P < 0.01	Pt. (n = 40) vs Ctrl. (n = 17)	Zhou et al[52]
					AUC = 0.773

AUC: Area under the receiver operating characteristic curve; BM: Bone marrow; EGC: Early gastric cancer; EGJ: Esophagogastric junction; GI: Gastrointestinal; MAH: Membrane-array hybridization; PA: Peripheral artery; PB: Peripheral blood; PV: Portal vein; SVC: Superior vena cava; TDB: Tumor-draining blood; N/A: Not available; qRT-PCR: Quantitative real-time polymerase chain reaction; FACS: Fluorescence activated cell sorter; ICC: Intracellular cytokine flow cytometry.