Abstract
BACKGROUND: The most practical serum biomarker AFP is negative in 80% patients with small tumor in the early stage of primary hepatocellular carcinoma (PHC). OBJECTIVE: To investigate significance of combined tests of serum golgi glycoprotein 73 (GP73), lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), glypican 3 (GPC3), des-gamma-carboxy prothrombin (DCP), CA199, ferritin (FER) and carcinoembryonic antigen (CEA) in diagnosis of small PHC with negative AFP. METHODS: A total of 50 cases of small PHC, 60 cases of non-PHC digestive system disorders and 40 cases of healthy controls were collected. Serum GP73, GPC3 and DCP were analyzed by enzyme-1inked immunosorbent assay. AFP-L3 was separated by microspincolumn; the levels of CA199, FER, CEA, AFP-L3 and total AFP were quantified by electrochemiluminescence immunoassays; percentage of AFP-L3 to total AFP was calculated. RESULTS: Levels of those biomarkers except FER were all significantly different among three groups (P < 0.01). Positive detection rates of seven biomarkers in PHC were higher than other groups (P < 0.01). In individual detection, the highest sensitivity, accuracy rate and area under ROC curve were 72.0%, 86.7% and 0.826 by GP73 and the highest specificity was 98.0% by GPC3. In combined detection with those seven biomarkers, the sensitivity, specificity, accuracy rate and area under ROC curve were 82.0%, 95.0%, 90.1% and 0.884. CONCLUSIONS: GP73 and AFP-L3 are superior biomarkers to aid the diagnosis of small PHC with negative AFP. The combined detection of biomarkers improved the diagnostic accuracy.