Role of circular RNAs in gastric cancer: Recent advances and prospects

Table 1 Deregulated circRNA in gastric cancer: function and potential signaling pathway

circRNA	Deregulation	Function/clinical association	Gene/pathway affected	Ref.
hsa_circ_0000993	Downregulation	Inhibits proliferation, migration and invasion	miR-214-5p	[23]
has_circ_0001461	Downregulation	Inhibits proliferation, migration and invasion; correlates with the clinical stage	miR-548g, RUNX1 in the cytoplasm; YBX1 in the nucleus	[24]
has_circ_0002320	Downregulation	Inhibits proliferation and invasion; correlates with TMN stage and survival time	miR-367-5p, p27	[25]
hsa_circ_0027599	Downregulation	Inhibits proliferation and migration; correlates with TNM stage	miR-101, PHLDA1	[26]
circRNA_100269	Downregulation	Inhibits proliferation; correlates with histological subtype,node invasive number and overall survival time	miR-630	[30]
circRNA_101057	Downregulation	Inhibits proliferation and invasion; correlates with tumor size and lymphatic metastasis and overall survival time	miR-424, LATS1	[31]
circZFR	Downregulation	Inhibits proliferation and promotes apoptosis	miR-130a/miR-107, PTEN	[35]
hsa_circ_0017639	Upregulation	Promotes proliferation; correlates with TNM stage	miR-182-5p, CREB1	[38]
circRNA_0000284	Upregulation	Promotes proliferation; correlates with T stage	miR-124 and miR-29b, COL1A1, COL4A1 and CDK6	[42]
circRNA_001569	Upregulation	Promotes proliferation and inhibits apoptosis; correlates with tumor size, depth of invasion and clinical stage	miR-145, NR4A2	[44]
circPDSS1	Upregulation	Promotes proliferation and inhibits apoptosis;correlates with worse overall survival time	miR-186-5p, NEK2	[45]
circNF1	Upregulation	Promotes proliferation	miR-16, MAP7 and AKT3	[49]
ciRS-7	Upregulation	Promotes proliferation and inhibits apoptosis; correlates with TNM stage and poor overall survival time	miR-7, PTEN/PI3K/AKT pathway	[53]

RUNX1: Runt-related transcription factor 1; YBX1: Y-box binding protein-1; PHLDA1: Pleckstrin homology like domain family A member 1; LATS1: Large tumor suppressor kinase 1; PTEN: Phosphatase and tensin homolog; CREB1: cAMP response element binding protein 1; COL1A1: Collagen type I α1 chain; COL4A1: Collagen type IV α1 chain; CDK6: Cyclin-dependent kinase 6; NR4A2: Nuclear receptor subfamily 4 group A member 2; NEK2: NIMA related kinase 2; MAP7: Microtubule associated protein 7.

Table 2 Deregulated circRNA in gastric cancer: diagnostic or predictive biomarker

circRNA	Deregulation	Cut-off value (ΔCt)	AUC	Sensitivity	Specificity	Clinical association	Ref.
hsa_circ_00000 96	Downregulation	12.9	0.82	-	-	Gender, invasion and TNM stage	[57]
hsa_circ_00001 81	Downregulation	9.4	0.756	85.2%	53.9%	Tumor diameter, lymphatic metastasis, distal metastasis, and CA19-9 (tissue)	[58]
		7.27	0.582	20.6%	99%	CEA and differentiation (plasma)
hsa_circ_00001 90	Downregulation	6.83	0.75	72.1%	68.3%	Tumor diameter, TNM stage and CA19-9 (tissue)	[59]
		3.07	0.6	41.4%	87.5%	CEA (plasma)
hsa_circ_00005 20	Downregulation	-	0.6129	53.57%	85.71%	TNM stage (tissue)	[60]
		-	0.8967	82.35%	84.44%	CEA (plasma)
hsa_circ_00007 45	Downregulation	-	0.683	85.5%	45%	Tumor differentiation (tissue) and TNM stage (plasma)	[61]
hsa_circ_00018 95	Downregulation	9.53	0.792	67.8%	85.7%	Tumor differentiation, Borrmann type, and tissue CEA	[62]
hsa_circ_00001649	Downregulation	0.227	0.834	71.1%	81.6%	Tumor differentiation	[63]
hsa_circ_002059	Downregulation	12.9	0.73	81%	62%	TMN stage, distal metastasis, gender and age	[64]
hsa_circ_00031 59	Downregulation	12.31	0.75	85.2%	56.5%	Gender, distal metastasis, and TMN stage	[65]
hsa_circ_00066 33	Downregulation	8.17	0.741	60%	81%	Distal metastasis and CEA	[66]
hsa_circ_00147 17	Downregulation	12.14	0.696	59.38%	81.25%	Tumor stage; distal metastasis; CEA; CA199	[67]
has_circ_00667 79	Downregulation	-	0.6726	90.3%	56.4%	TNM stage overall survival time	[68]
hsa_circ_00743 62	Downregulation	12.17	0.63	84.3%	36.2%	CA19–9 and lymphatic metastasis	[69]
hsa_circ_01308 10	Downregulation	1.443	0.7481	77.42%	68%	TNM stage and overall survival time	[70]
hsa_circ_00004 67	Upregulation	-	0.79	70.5%	64.8%	TNM stage	[71]
hsa_circ_00176 39	Upregulation	11.46	0.7585	80.56%	63.89%	TNM stage	[38]
hsa_circ_00664 44	Upregulation	-	0.7328	70.75%	68.87%	Lymphatic metastasis	[72]

AUC: Area under the curve; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.