Biomarkers for the early diagnosis of hepatocellular carcinoma

Table 1 Phases of biomarker validation for early cancer detection

Phase of biomarker validation	Type of study	Aim	Biomarker
Phase I	Preclinical exploratory	Identify promising markers
Phase II	Case-control	Clinical assay to detect HCC	AFP-L3, DCP, GPC3, OPN, GP73, SCCA, annexin A2
			suPAR, MDK, AXL, TRX, nucleic acids, miRNA
Phase III	Retrospective longitudinal	Characterize ability of biomarker to detect HCC before it becomes clinical
Phase IV	Prospective screening	Identify extent and characteristics of sensitivity and specificity
Phase V	Randomized control	Determine if biomarker screening can reduce mortality in target population	AFP

Table 2 Early diagnostic values of hepatocellular carcinoma serum biomarkers

Biomarker	Sensitivity, % (95%CI)	Specificity, % (95%CI)	Ref.
AFP	53 (46-59)	90 (87-93)	[17]
AFP-L3	28 (22-34)	97 (93-100)	[17]
DCP	61 (55-68)	70 (65-74)	[17]
GPC3	55.1 (47.9-66.2)	97.0 (95.2-98.2)	[42]
OPN	75 (58-93)	62 (51-73)	[50]
GP73	62	88	[56]
miRNA panel1	82.5	83.5	[101]

¹Including miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801.