Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

Table 1 Deregulated miRNA in gastric cancer tumor

miRNA/role	Targets	Clinicopathological features	Ref.
OncomiRNAs
miR-17	UBE2C	Tumor size	[21-24]
	FBXO31	Tumor infiltration
		Clinical grade
		Prognosis
		Tumor stage
mir-19a	MXD1	Migration	[25-28]
	SOCS1	Invasion
	PTEN	Metastasis
		Proliferation
		Multidrug resistance
miR-20a	EGR2	Overall survival	[29-31]
	E2F1	Relapse-free survival
		Self-renewal and proliferation of GC stem cells
		Chemoresistance of GC cells to cisplatin and docetaxel
miR-21	PTEN	Differentiation	[29,32-37]
	PDCD4	Lymph node metastasis
	RECK	H. pylori infection
	SERPINI1	Tumor stage
		Tumor size
miR-25	FBXW7	Proliferation	[38-41]
	TOB1	Invasion
	RECK	Migration
		Metastasis
		Aggressive phenotype
		Poor long-term survival
miR-27a	PHB	H. pylori infection	[42-44]
	ZBTB10	Proliferation
	HOXA10	Drug resistance
	CCND1
miR-106a	TIMP2	Invasion	[45-50]
	PTEN	Differentiation
	FAS	Distant metastasis
	RUNX3	Lymph node metastasis
		Tumor stage
		Tumor size
miR-106b	P21	Lymph node metastasis	[29,46,51-54]
	E2F5	Depth of infiltration
	E2F1
miR-200b	ZEB1	Diffuse-type	[55-58]
	ZEB2	Poor overall survival
	SUZ12	H. pylori infection
	DNMT3A	Metastasis
	DNMT3B	Tumor size
	SP1
	WNT-1
miR-215	RB1	Tumor stage	[59-61]
	RUNX1
miR-222	PTEN	Shorter metastasis-free survival	[38,62-65]
	RECK	Proliferation
tsmiRNAs
let-7a	RAB40C	Differentiation	[66-71]
	CDKN1	Lymph node metastasis
	SPHK2	Cell cicle arrest
	FN1	Growth suppression
		Overall survival
		Relapse-free survival
miR-143	COX-2	Invasion	[69,72-75]
		Haematogenous metastasis
		Lymph node metastasis
		Tumor stage
miR-148a	ROCK1	Clinical stage	[76-80]
	MMP7	Lymph node metastasis
	p27	Poor clinical outcome
	DNMT1	Epithelial-mesenchymal transition
	SMAD4
miR-200c	RND3	Lymph node metastasis	[56,57,81,82]
	DNMT3A	Poor overall survival
	DNMT3B	Sensitivity of chemotherapy to cisplatin
	SP1	Clinical stage
		Invasion
miR-204	SIRT1	Epithelial-mesenchymal transition	[83-85]
	BCL-2	Anoikis resistance
	EZR	Migration
		Invasion
		Colony forming ability
miR-218	VOPP1	Proliferation	[86-89]
	ROBO1	Migration
		Metastasis
miR-433	RAB34	Tumor stage	[90-92]
	KRAS	Overall survival
		Proliferation
		Migration
		Invasion
Controversial
miR-9	CCND1	Proliferation	[90,93-96]
	ETS1	Invasion
	CDX2	Metastasis
	GRB2
	NF-kappaB1
	RAB34
miR-107	FOXO1	Invasion	[97-100]
	DICER1	Differentiation
	CDK6	Lymph node metastasis
		Tumor size
		Tumor stage
		Overall survival
miR-146a	EGFR	Tumor size	[101-106]
	IRAK1	Poor differentiation
	L1CAM
	CARD1O	Lymph node metastasis
	COPS8	Venous invasion
	NASF2	Overall survival time
	SMAD4	Apoptosis
	WASF2
miR-155	SMAD2	Invasion	[38,107-111]
	CDC73	Lymph node metastasis
	CYCLIN D1	H. pylori infection
		Cell viability
		Apoptosis
miR-181b	CREB1	Proliferation	[112-115]
	BCL2	Migration
		Invasion
		Colony formation
		Apoptosis
		Multidrug resistance
miR-223	EPB4IL3	Poor metastasis-free survival	[116-118]
	STMN1	Apoptosis
	FBXW7	Proliferation
		Invasion
	HMGA2	Poor clinical prognosis

Table 2 Circulating miRNA as diagnostic and prognostic biomarkers

miRNA	Samples	Potential biomarker type	Method	Clinical implication	Ref.
miR-1	164 GC/127 C Serum	Diagnostic	Solexa sequencing	GC detection	[128]
			qRT-PCR
miR-16	40 GNCA/40 C Plasma	Diagnostic	Taqman low-density array	Early detection of GNCA	[122]
			qRT-PCR
miR-17-5p	79 GC/30 C Plasma	Diagnostic	qRT-PCR	GC detection	[46]
	79 pre-operative GC/30 post-operative GC/6 relapse Plasma	Prognostic	qRT-PCR	Prediction of prognosis and monitoring of chemotherapeutic effects	[129]
miR-18a	104 GC/65 C Plasma	Diagnostic	qRT-PCR	Screening GC and monitoring tumor dynamics	[130]
		Prognostic
miR-20a	164 GC/127 C Serum	Diagnostic	Solexa sequencing	GC detection	[128]
			qRT-PCR
	90 GC/90 C Plasma	Diagnostic	qRT-PCR	Early detection of GC	[131]
	79 pre-operative GC/30 post-operative GC/6 relapse Plasma	Prognostic	qRT-PCR	Prediction of prognosis and monitoring of chemotherapeutic effects	[129]
miR-21	69 GC Plasma	Prognostic	qRT-PCR	Prognostic marker	[132]
	16 LN-metastasis positive/15 LN-metastasis negative/10 C Serum	Prognostic	qRT-PCR	Predicting LN metastasis	[133]
	79 GC/30 C Plasma	Diagnostic	qRT-PCR	GC detection	[46]
	70 GC/70 C Plasma	Diagnostic	qRT-PCR	GC detection	[134]
miR-25	40 GNCA/40 C Plasma	Diagnostic	Taqman low-density array	Early detection of GNCA	[122]
			qRT-PCR
miR-34	164 GC/127 C Serum	Diagnostic	Solexa sequencing	GC detection	[128]
			qRT-PCR
miR-92a	40 GNCA/40 C Plasma	Diagnostic	Taqman low-density array	Early detection of GNCA	[122]
			qRT-PCR
miR-106a	79 GC/30 C Plasma	Diagnostic	qRT-PCR	GC detection	[46]
miR-106b	79 GC/30 C Plasma	Diagnostic	qRT-PCR	GC detection	[46]
	90 GC/90 C Plasma	Diagnostic	qRT-PCR	Early detection of GC	[131]
miR-191	57 GC/58 C Serum	Diagnostic	qRT-PCR	GC detection	[135]
miR-218	70 GC/70 C Plasma	Diagnostic	qRT-PCR	GC detection	[134]
miR-221	90 GC/90 C Plasma	Diagnostic	qRT-PCR	Early detection of GC	[131]
miR-223	70GC/70C Plasma	Diagnostic	qRT-PCR	GC detection	[134]
miR-378	61GC/61C Serum	Diagnostic	miRNA microarray	Early detection of GC	[136]
			qRT-PCR
miR-423-5p	164GC/127C Serum	Diagnostic	Solexa sequencing	GC detection	[128]
			qRT-PCR
miR-451	56GC/30C Plasma	Diagnostic	miRNA microarray	Screening GC	[137]
			qRT-PCR
	40GNCA/40C Plasma	Diagnostic	Taqman low-density array	Early detection of GNCA	[122]
			qRT-PCR
miR-486	56GC/30C Plasma	Diagnostic	miRNA microarray	GC Screening	[137]
			qRT-PCR
miR-486-5p	40GNCA/40C Plasma	Diagnostic	Taqman low-density array	Early detection of GNCA	[122]
			qRT-PCR
let-7a	79GC/30C Plasma	Diagnostic	qRT-PCR	GC detection	[46]

C: Control; GC: Gastric cancer; LN: Lymph node; GNCA: Gastric non-cardia adenocarcinoma; qRT-PCR: Quantitative real time polymerase chain reaction.

Table 3 miRNA related to the risk of gastric cancer

miRNA	SNP	Country	Population	Number of cases/controls	Ref.
miR-27a	rs895819	China	Asian	304/304	[43]
		China	Asian	295/413	[154]
		China	Asian	278/278	[155]
	rs11671784	China	Asian	892 /978	[156]
		China	Asian	278/278	[155]
miR-146a	rs2910164	China	Asian	304/304	[157]
		Japan	Asian	583/1637	[158]
		Japan	Asian	90/90	[101]
		China	Asian	1686/1895	[159]
		South Korea	Asian	461/447	[160]
		Japan	Asian	552/697	[161]
miR-196a	rs11614913	Japan	Asian	552/697	[161]
		China	Asian	213/213	[162]
		South Korea	Asian	461/447	[160]
		Greece	Greak	163/480	[163]
miR-499	rs3746444	Japan	Asian	697/552	[161]
		South Korea	Asian	461/447	[160]
		China	Asian	363/969	[164]
miR-149	rs2292832	China	Asian	274/269	[165]
		South Korea	Asian	461/447	[160]
		Greece	Greak	163/480	[163]
miR-24	rs4819388	China	Asian	183/348	[166]
miR-570	rs4143815	China	Asian	205/393	[167]
miR-200c	rs12904	China	Asian	522/501	[168]
miR-505	rs111638916	China	Asian	857/748	[169]
Pre-miR-30c	rs928508	China	Asian	240/240	[170]
Pri-let-7a-2	rs629367	China	Asian	107/124	[171]