Emerging blood-based biomarkers for detection of gastric cancer

Table 4 Cell-free RNAs as biomarkers for detection of gastric cancer

Candidate biomarkers	Sample size and type	Method/technology	Diagnostic value/outcome	Ref.
Circulating cell-free miRNAs
miR-106a/let-7a ratio	GC = 69, HC = 30; plasma	qRT-PCR	AUC = 0.879, Sn = 85.5%, Sp = 80%	Tsujiura et al[117], 2010
5-miRNA signature: miR-1, miR-20a, miR-27a, miR-34, miR-423-5p	Discovery: GC = 20, HC = 20; Validation: GC = 142, HC = 105; Serum	Discovery: Solexa sequencing; Testing: qRT-PCR	AUC = 0.831 (validation set)	Liu et al[155], 2011
miR-451	Discovery: pre- and post-operative plasma, GC = 3; Validation: GC = 56, HC = 30	Discovery: microarray	AUC = 0.96, Sn = 96%, Sp = 100%; decreased in 90% of post-operation plasma samples	Konishi et al[119], 2012
miR-486		Testing: qRT-PCR	AUC = 0.92, Sn = 86%, Sp = 97%; decreased in 93% of post-operation plasma samples
miR-378	Discovery: GC = 7, CRC = 7, HC = 10;	Discovery: microarray	AUC = 0.861, Sn = 87.5%, Sp = 70.73%;	Liu et al[122], 2012
	Validation: GC = 40, HC = 41; serum	Testing: qRT-PCR	No significant differences across stages I-IV
miR-223	Test set: GC = 10, HC = 10; Validation: GC = 60, HC = 60; plasma	qRT-PCR	AUC = 0.9089	Li et al[121], 2012
miR-21			AUC = 0.7944
miR-218			AUC = 0.7432
3 miRNA combined			AUC = 0.9531, Sn = 84.29%, Sp = 92.86%
			No significant differences across stages I-IV
3-miRNA signature: miR-221, miR-744, and miR-376c	Discovery: GC = 14, HC = 14;	Discovery: TaqMan array, validation: qRT-PCR	Sn = 82.4%, Sp = 58.8% (for GC vs HC)	Song et al[124], 2012
	Validation I: GC = 68, HC = 68		Sn = 73.3% (for early GC)
	Validation II: DYS = 46, HC = 46		miR-221 elevated in DYS, no difference from HC for miR-376c and miR-744;
	Pre-diagnosis serum samples, GC = 58		Increase during GC development;
			Sn = 79.3% (for GC 2-5 years before diagnosis)
miR-106b	Discovery: GC = 30, HC = 30	qRT-PCR	AUC = 0.773 (all in validation set)	Cai et al[156], 2013
miR-20a	Validation: GC = 60, HC = 60;		AUC = 0.859
miR-221	plasma		AUC = 0.796
miR-223	GC = 50, HC = 47; serum	qRT-PCR	AUC = 0.85, Sn = 81%, Sp = 78%;	Wang et al[157], 2014
			Increased in advanced stages
miR-16			AUC = 0.90, Sn = 79%, Sp = 78%
miR-100			AUC = 0.71, Sn = 71%, Sp = 58%
			Increased in advanced stages
miR-16	Discovery: stage I non-cardia GC = 40, HC = HC; Validation: stage I non-cardia GC = 48, HC = 102	Discovery: TaqMan array, validation: qRT-PCR	AUC = 0.768 (all in validation set)	Zhu et al[120], 2014
miR-25			AUC = 0.694
miR-92a			AUC = 0.732
miR-451			AUC = 0.790
miR-486-5p			AUC = 0.779
5 miRNA combined			AUC = 0.812, Sn = 72.9%, Sp = 89.2%; In vitro evidence that miR-16, miR-25 and miR92a but not miR-451 and miR486-5p are secreted from cancer cells
miR-222	GC = 114, HC = 56; plasma	qRT-PCR	AUC = 0.850, Sn = 66.1%, Sp = 88.3%	Fu et al[158], 2014
miR-18a	GC = 82, HC = 65, plasma	qRT-PCR	AUC = 0.907, Sn = 80.5%, Sp = 84.6%; no association with stage	Su et al[123], 2014
miR-18a	GC = 104, HC = 65, plasma and GC tissues	qRT-PCR	AUC = 0.8059, Sn = 84.6%, Sp = 69.2%	Tsujiura et al[159], 2015
			Overexpressed in GC; in vitro evidence that miR-18a is released by cancer cells; decreased in postoperative plasma
Circulating cell-free mRNAs and long non-coding RNAs
hTERT mRNA	GC = 118, CAG = 40, HC = 58; plasma	qRT-PCR	AUC = 0.891, Sn = 66%, Sp = 87%; strong positive correlation with advanced stage of GC	Kang et al[125], 2013
MACC1 mRNA	GC = 76, HC = 54, plasma	qRT-PCR	Sn = 68%, Sp = 89%	Burock et al[160], 2015
LINC00152	Pre- and post-operative plasma GC = 79, GED = 31, HC = 81	qRT-PCR	AUC = 0.657, Sn = 48.1%, Sp = 85.2%	Li et al[131], 2015

AUC: Area under the curve; DYS: Intestinal dysplasia; GC: Gastric cancer; HC: Healthy controls; Sn: Sensitivity; Sp: Specificity.