Emerging blood-based biomarkers for detection of gastric cancer

Table 3 Cell-free DNA as biomarkers for detection of gastric cancer

Candidate biomarkers	Sample size and type	Method/technology	Diagnostic value/outcome	Ref.
Total cell-free DNA level
β-actin (total cf DNA level)	GC = 53, HC = 21, plasma	qPCR	AUC = 0.75, P < 0.0001	Sai et al[90], 2007
DNA integrity		qPCR (ratio of long vs short b-actin amplicons)	No significant difference between GC and HC
Alu DNA sequences	GC = 54, HC = 59; plasma	Alu81-qPCR	AUC = 0.784, Sn = 75%, Sp = 63%	Park et al[91], 2012
Total cfDNA level	Early GC = 16; advanced GC = 14; HC = 34; plasma	Measurement of cfDNA concentration	AUC = 0.991, Sn = 96.67%, Sp = 94.11% for GC vs HC	Kim et al[92], 2014
Gene amplification
MYC gene copy number (MYC/GAPDH ratio)	GC = 57, HC = 39; tissues and plasma	qPCR	AUC = 0.816; strong positive correlation between MYC levels in GC tissues and plasma (r = 0.342; P = 0.009)	Park et al[99], 2009
HER2 gene copy number (HER2/RPPH1 ratio)	Discovery: GC = 52 (pre and post-operative treatment), HC = 40; plasma and tissues	qPCR	AUC = 0.746, Sn = 53.9%, Sp = 96.7%; Positive correlation between GC tissues and plasma (r = 0.424; P = 0.00721); decrease in post-treatment plasma in HER2 + GC cases	Shoda et al[100], 2014
	Validation: GC = 25 plasma		Sn = 66.7%, Sp = 100%
DNA methylation markers
RPRM (Reprimo)	GC = 43, HC = 31; GC tissues and plasma	MSP	95.3% GC, 9.7% HC, P < 0.00001; Strong correlation between methyl status in tissues and plasma	Bernal et al[107], 2008
RUNX3	GC (preoperative) = 65, GC (postoperative) = 43, HC = 50, tissues and serum	qMSP	AUC = 0.8651, Sn = 95.5%, Sp = 62.5%; decrease after surgical resection	Sakakura et al[152], 2009
KCNA4 + CYP26B1	GC = 46, GPL = 46, HC = 30; serum	Discovery: Methylation microarray in tissues; Testing: MSP	AUC = 0.917, Sn = 91.3%, Sp = 92.1%	Zheng et al[109], 2011
SLC19A3	Discovery: GC = 45, HC = 60; plasma	MSRED-qPCR	Increased in GC, P < 0.0001	Ng et al[153], 2011
	Validation: GC = 20, HC = 20		AUC = 0.82, Sn = 85%, Sp = 85%
FAM5C + MYLK	GC = 58, GPL = 46, HC = 30; serum	Discovery: MeDIP in cell lines; Testing: MSP	AUC = 0.838, Sn = 77.6%, Sp = 90% for GC vs HC; Sn = 30.4% for GPL vs HC; decrease after surgical resection	Chen et al[154], 2012
XAF1	GC = 202, HC = 88, tumor tissues and serum	qMSP	AUC = 0.909, P < 0.0001; 83.9% concordance between GC tissues and serum	Ling et al[108], 2013

AUC: Area under the curve; GC: Gastric cancer; GPL: Gastric precancerous lesions; HC: Healthy controls; MeDIP: Methylated DNA immunoprecipitation; MSP: Methylation-specific PCR; MSRED-qPCR: Methylation-sensitive restriction enzyme digestion and real-time quantitative PCR; Sn: Sensitivity; Sp: Specificity.