Systematic Review and Meta-Analysis of the Utility of Circular RNAs as Biomarkers of Hepatocellular Carcinoma

Table 1

Altered circRNAs expression associated with clinicopathological features of HCC in 23 eligible articles.

Study	Sample size	circRNA	Altered expression	Test Method	Specimen	Co-variants; (clinicopathological parameters)	Function	Reference
Zhang 2018	73/104	hsa_circ_0001445	Down	qRT-PCR	Tissue	Tissue: Tumor foci; Spasm: AFP	Apoptosis/proliferation/; migration/invasion	[22]
					Spasm
Zhang 2018	86	circSMAD2	Down	qRT-PCR	Tissue	Differentiation	Migration/invasion/ EMT	[23]
Qin 2016	89	Hsa_circ_0001649	Down	qRT-PCR	Tissue	tumor size and embolus	Metastasis	[8]
Fu 2017	81	Hsa_circ_0005986	Down	qRT-PCR	Tissue	BCLC stage, chronic hepatitis B, tumor size, MVI	Carcinogenesis	[24]
Fu 2017	102	hsa_circ_0004018	Down	qRT-PCR	Tissue	AFP, tumor size, differentiation, BCLC and TNM stage	Carcinogenesis/metastasis	[25]
Chen 2018	78	hsa_circ_0128298	Up	qRT-PCR	Tissue	vascular cancer embolus, lymphatic metastasis and organ metastasis	Proliferation/metastasis	[26]
Yao 2017	102	cirZKSCAN1	Down	qRT-PCR	Tissue	tumor number, liver cirrhosis, vascular invasion and TNM stage	Growth/migration/invasion	[27]
Huang 2017	80	circRNA_100338	Up	qRT-PCR	Tissue	Vascular invasion, Lung metastasis and TNM stage	Metastasis	[28]
Chen 2018	50	circHIPK3	Up	qRT-PCR	Tissue	TNM stage, differentiation, HBV-DNA copy numbers and liver cirrhosis	Proliferation/migration	[29]
Jin 2017	30	Hsa_circ_001569	Up	qRT-PCR	Tissue	tumor differentiation and TNM stage	Proliferation/ growth	[30]
Shang 2016	30	hsa_circ_0005075	Up	qRT-PCR	Tissue	tumor size	Proliferation/invasion/; metastasis	[31]
Yu 2018	163	cSMARCA5	Down	qRT-PCR	Tissue	Tumor size, differentiation, TNM stage, BCLC stage, Edmondson’s grade and MVI	Growth/metastasis	[9]
Fu 2018	107	hsa_circ_0003570	Down	qRT-PCR	Tissue	tumor size, differentiation, AFP, MVI, BCLC stage and TNM stage	Recurrence/metastasis	[32]
Yao 2018	100	hsa_circ_0068669	Down	qRT-PCR	Tissue	MVI and TMN stage	Progression	[33]
Zhong 2018	47	CircC3P1	Down	qRT-PCR	Tissue	TNM stage, tumor size and vascular invasion	Proliferation/migration/; invasion	[34]
Zhang 2018	77	hsa_circ_0001649	Down	qRT-PCR	Tissue	No significant correlation	Apoptosis/proliferation/; migration/invasion	[35]
Zhu 2018	46	circ-PV T1	Up	qRT-PCR	Tissue	Tumor size, differentiation and TNM stage	Proliferation	[36]
Meng 2018	75	circ-10720	Up	FISH	Tissue	Tumor stage, AFP and HBV markers	Development/progression	[37]
Li 2018	51	circRNA101368	Up	qRT-PCR	Tissue	Tumor size, distant metastasis and TNM stage	Migration	[38]
Liu 2018	70	circ_001569	Up	qRT-PCR	Tissue	Tumor size and TNM stage	Growth/metastasis	[39]
Weng; 2018	120	hsa_circ_0064428	Down	qRT-PCR	Tissue	Tumor size, differentiation and TNM stage	Tumourigenesis/metastasis	[40]
Xie 2018	56	has_circ_0078710	Up	qRT-PCR	Tissue	TNM stage	Proliferation/migration/; invasion/growth	[41]
Gong 2018	64	circ-ZEB1.33	Up	qRT-PCR	Tissue	Tumor size and TNM stage	Proliferation	[42]
					serum

EMT: epithelial-mesenchymal transition; BCLC: Barcelona Clinic Liver Cancer Staging System; AFP: alpha-fetoprotein; TNM: tumor-node-metastasis; MVI: microvascular invasion; FISH: fluorescence in situ hybridization; HBV: hepatitis B virus.