Clinical significance of exosomes as potential biomarkers in cancer

Table 1 Studies included for meta-analysis of exosomal biomarkers in cancer diagnosis

Ref.	Country	Cancer type	Stage	Control	Number of Control	Number of patients	Sample	Isolation method of exosome	Marker	Detection method	Cut-off	TP	TN	FP	FN
Sun et al[35]	China	Colorectal	All	Healthy	32	92	Plasma	UC	CPNE3	ELISA	0.143 pg/μg exosome	62	27	5	30
Ogata-Kawata et al[36]	Japan	Colorectal	All	Healthy	11	88	Serum	UC	miR-1246	qRT-PCR	1.45	84	10	4	1
									miR-23a		0.3100	81	11	7	0
									miR-21		1.08	54	10	34	1
									miR-150		0.08	49	11	39	0
									let-7a		0.9	44	10	44	1
									miR-223		1.72	41	10	47	1
									miR-1224-5p		0.5	28	11	60	0
									miR-1229		0.06	20	11	68	0
Liu et al[37]	China	Colorectal	All	Healthy and benign	320	148	Serum	ExoQuick	CRNDE-h	qRT-PCR	0.02	104	302	18	44
Uratani et al[38]	Japan	Colorectal	NR	Healthy	47	26	Serum	ExoQuick	miR-21	qRT-PCR	Youden index	18	38	9	8
Lin et al[39]	China	Gastric	All	Healthy	60	51	Plasma	UC	lncUEGC1	qRT-PCR	NR	45	50	10	6
									lncUEGC2		NR	46	34	26	17
Zhao et al[40]	China	Gastric	All	Healthy	120	126	Serum	NR	HOTTIP	qRT-PCR	1.72	88	102	18	38
Pang et al[41]	China	Gastric	All	Healthy	37	40	Serum	ExoQuick	ZFAS1	qRT-PCR	NR	32	28	9	8
Yang et al[42]	China	Gastric	All	Healthy	80	80	Serum	ExoQuick	miR-423-5p	qRT-PCR	NR	65	46	34	15
Goto et al[43]	Japan	Pancreatic	All	Healthy and advanced pancreatic cancer	22	23	Serum	ExoQuick	miR-191	qRT-PCR	Distance = (1-sensitivity)2 + (1-specificity)2 in ROC curve	18	17	5	5
									miR-21			20	18	4	3
									miR-451a			16	18	4	7
Melo et al[44]	Germany	Pancreatic	All	Healthy	100	190	Serum	UC	GPC1	Flow cytometry	Youden index	190	100	0	0
Que et al[45]	China	Pancreatic	All	Non-PDAC	27	22	Serum	UC	miR-17-5p	qRT-PCR	6.826	20	20	7	2
									miR-21		7.693	18	26	1	4
Machida et al[46]	Japan	Pancreatobiliary tract	II-IV	Healthy	13	12	Saliva	Total exosome isolation kit	miR-1246	qRT-PCR	13.77	8	13	0	4
									miR-4644		-5.205	9	10	3	3
Xu et al[47]	China	Liver	All	Chronic hepatitis B	68	88	Serum	Total exosome isolation kit	hnRNPH1	qRT-PCR	0.67	75	52	16	13
Sun et al[48]	China	Liver	All	Healthy	56	56	Serum	Total exosome isolation kit	LINC00161	qRT-PCR	NR	42	41	15	14
Xu et al[49]	China	Liver	All	Chronic hepatitis B	96	60	Serum	Total exosome isolation kit	ENSG00000258332.1	qRT-PCR	1.345	43	80	16	17
					60	55			ENSG00000258332.1		1.366	40	48	12	15
					96	60			LINC00635		1.69	46	75	21	14
					60	55			LINC00635		1.532	44	45	15	11
Goldvaser et al[50]	Israel	Pan-cancer (not include liver)		Healthy	45	98	Serum	Total exosome isolation kit	hTERT	qRT-PCR	NR	61	45	0	37
		Liver	NR	Healthy	45	35					NR	21	45	0	14
Zhang et al[51]	China	Lung	All	Healthy	30	77	Serum	ExoQuick	MALAT-1	qRT-PCR	NR	62	21	9	15
Sun et al[52]	China	Lung	All	Healthy	15	15	Plasma	UC	14-3-3ζ	ELISA		9	12	3	6
Li et al[53]	NR	Ovarian		Benign	21	50	Serum	UC	ephrinA2	ELISA	20.4 ng/L	44	17	4	6
Meng et al[54]	NR	Ovarian	All	Benign	20	163	Serum	Total exosome isolation kit	miR-200a	PCR+ qRT-PCR	Youden index	135	18	2	28
									miR-200b			86	20	0	77
									miR-200c			51	20	0	112
Pan et al[55]	Germany	Ovarian	All	Healthy	29	106	Plasma	ExoQuick	miR-21	PCR+ qRT-PCR	Youden index	65	24	5	41
									miR-100			66	21	8	40
									miR-200b			68	25	4	38
									miR-320			59	20	9	47
Bryzgunova et al[56]	Russia	Prostate	All	Healthy	20	14	Urine	UC	miR-125	qRT-PCR	NR	12	13	7	2
									miR-19b		NR	11	19	1	3
Wang et al[57]	China	Prostate	II-IV	Healthy	30	34	Plasma	Total exosome isolation kit	SAP30L-AS1	qRT-PCR	NR	21	25	5	13
									SChLAP1		NR	30	23	7	4
Øverbye et al[58]	NR	Prostate	All	Healthy	15	16	Urine	UC	ADIRF	Mass spectrometry	Youden index	12	16	0	3
									TMEM256			14	16	0	1
Işın et al[59]	NR	Prostate	All	BPH	49	30	Urine	Urine Exosome RNA Isolation Kit	LincRNA-p21	qRT-PCR	0.181	20	31	18	10
Wang et al[60]	China	Laryngeal	All	Vocal cord polyps	49	52	Serum	ExoQuick	miR-21	qRT-PCR	0.043	36	40	9	16
									HOTAIR		0.032	48	28	21	4
Alegre et al[61]	NR	Melanoma	NR	Healthy	25	53	Serum	ExoQuick	exo-MIA	ELISA	1.4 μg/L	42	20	5	11
									exo-S100B	ELISA	0.015 μg/L	42	20	5	11
Manterola et al[62]	France	GBM	NR	Healthy	30	50	Serum	ExoQuick	RNU6	qRT-PCR	0.372	33	20	10	17
Chen et al[63]	Taiwan	Bladder	All	hernia	81	140	Urine	UC	TACSTD2	ELISA	2.47 ng/mL	103	62	19	37
Ge et al[64]	China	Cholangiocarcinoma	All	Biliary obstruction	56	35	Bile	UC	ENST00000588480.1	qRT-PCR	NR	22	41	15	13

UC: Ultracentrifugation; NR: Not reported.