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

Table 5 Circulating cell-free microRNA/long non-coding RNA in gastric cancer

Characteristic and number of patients		Controls (n)	Plasma/serum	Detection method		Detection rate/statistic value				Ref.
microRNA
I-IV	69	30	Plasma	qRT-PCR	miR-17-5p↑	P = 0.05		Pt. (n = 69) vs Ctrl (n = 30)	(a)	Tsujiura et al[124]
					miR-21↑	P = 0.006		Pt. (n = 69) vs Ctrl (n = 30)	(a)
						P = 0.013		paired (n = 10), pre-op > post-op	(b)
					miR-106a↑	P = 0.008		Pt. (n = 69) vs Ctrl (n = 30)	(a)
					miR-106b↑	P < 0.001	AUC = 0.721	Pt. (n = 69) vs Ctrl (n = 30)	(a)
						P = 0.022		paired (n = 10), pre-op > post-op	(b)
					let-7a↓	P = 0.002		Pt. (n = 69) vs Ctrl (n = 30)	(a)
					miR-106a/let-7a↑		AUC = 0.879
I-IV	164	127	Serum	Solexa sequencing	miR-1↑	P < 0.01	Pt. (n = 164) vs Ctrl (n = 127)		(a)	Liu et al[177]
				qRT-PCR	miR-20a↑	P < 0.01			(a)
					miR-27a↑	P < 0.01			(a)
					miR-34a↑	P < 0.01			(a)
					miR-423-5p↑	P < 0.01			(a)
					Five-serum miRNA signature↑	AUC = 0.879	Pt. (n = 22) vs Ctrl (n = 22) (test study)
						AUC = 0.831	Pt. (n = 142) vs Ctrl (n = 105) (validation study)
I-IV	56	30	Plasma	Microarray	miR-451↑	P < 0.01	AUC = 0.96	Pt. (n = 56) vs Ctrl (n = 30)	(a)	Konishi et al[125]
				qRT-PCR		P < 0.01		paired (n = 29), pre-op > post-op	(b)
					miR-486↑	P < 0.01	AUC = 0.92	Pt. (n = 56) vs Ctrl (n = 30)	(a)
						P < 0.01		paired (n = 29), pre-op > post-op	(b)
I-IV	40	41	Serum	Microarray	miR-187*↑	P = 0.0016	AUC = 0.704	Pt. (n = 40) vs Ctrl (n = 41)	(a)	Liu et al[178]
				qRT-PCR	miR-371-5p↑	P = 0.0009	AUC = 0.715		(a)
					miR-378↑	P < 0.0001	AUC = 0.861		(a)
N/A	82	82	Serum	Microarray	miR-221↑	AUC = 0.74	Pt. (n = 68) vs Ctrl (n = 68) (second validation study)			Song et al[179]
				qRT-PCR	miR-376c↑	AUC = 0.71
					miR-744↑	AUC = 0.71
N/A	20		Serum	qRT-PCR	miR-196a	P = 0.012	Pre-op (n = 20) > post-op (n = 20)		(a)	Tsai et al[180]
(pre-op, post-op and recurrent)						P = 0.002	Post-op (n = 20) < at recurrent (n = 20)		(a)
I-IV	30	39	Serum	qRT-PCR	miR-21↑	P < 0.001	AUC = 0.81	Pt. (n = 30) vs Ctrl (n = 39)	(a)	Wang et al[181]
I-IV	87		Plasma	qRT-PCR	miR-17-5p↑	P < 0.001		Pre-op (n = 65) > post-op (n = 16)	(a)	Wang et al[182]
	(65 pre-op)					P = 0.003		Post-op (n = 16) < recurrent (n = 6)	(a)
	(16 post-op)					OS: P = 0.0003	miR-17-5p high vs low	Pre-op (n = 65)	(c)
	(6 recurrent)				miR-20a↑	P = 0.006		Pre-op (n = 65) > post-op (n = 16)	(a)
						OS: P = 0.0003	miR-20a high vs low	Pre-op (n = 65)	(c)
						OS: P = 0.013	miR-20a high vs low	pre-op (n = 65)	(d)
I-IV	20	20	Serum	miRNA microarray	miR-375↓	P < 0.001	AUC = 0.835	Pt. (n = 20) vs Ctrl (n = 20)	(a)	Zhang et al[183]
				qRT-PCR
	20	190	Plasma	miRNA microarray	miR-195-5p↓	P < 0.05	Fold changes 13.3	Pt. (n = 20) vs Ctrl (n = 130)	(a)	Gorur et al[184]
I-III	79				miR-21↑	P < 0.001	Correlation with pN stage		(e)	Kim et al[185]
(25 without LN meta)					miR-146a↑	P = 0.001	Correlation with pN stage		(e)
(54 with LN meta)					miR-148a↑	P < 0.001	Correlation with pN stage		(e)
I-IV	69		Plasma	qRT-PCR	miR-21↑	CSS: P = 0.0451	miR-21 high vs low		(c)	Komatsu et al[186]
						CSS: P = 0.0133			(d)
I-II	80	70	Plasma	qRT-PCR	miRNA-199a-3p↑	P < 0.001	AUC = 0.818	Pt. (n = 80) vs Ctrl. (n = 70)	(a)	Li et al[187]
		(healthy controls)				P = 0.004	Pt. (n = 80) vs pancreous disease (n = 20)		(a)
		20				P = 0.012	Pre-op > post-op (n = 30)		(b)
		(precancerous disease)
Long non-coding RNA
I-IV	43	33	Plasma	qRT-PCR	H19	P = 0.029		Pt. (n = 43) vs Ctrl. (n = 33)	(a)	Arita et al[128]
					HOTAIR	P = 0.096			(a)
					MALAT1	P = 0.14			(a)

a: Unpaired t-test/Mann-Whitney U-test; b: Wilcoxon test; c: Kaplan-Meier survival curves, Log-rank test; d: Logistic regression model (multivariate); e: Kruskal-Wallis test. AUC: Area under the receiver operating characteristic curve; CSS: Cause-specific survival; LN: Lymph node; N/A: Not available; qRT-PCR: Quantitative real-time polymerase chain reaction; OS: Overall survival.