The Diagnostic Value Of Serum Egf17, A Novel Serological Marker, For Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most serious malignancy tumors threatening human health. Early detection with early treatment is very critical for the treatment of HCC. However, most popular serum markers, which have been widely used for HCC, can not correctly detect all disorders. Studies show that Epidermal growth factor-like domain 7 (Egfl7) may play a role in HCC angiogenesis, which is a highly vascular tumor characterized by neovascularization. Egfl7 may be a novel serological diagnostic marker as a secreted protein.Objective: In this study, we establish a sandwich ELISA method to detect the serum concentration of Egfl7 in order to identify whether Egfl7 is a novel serological marker for HCC or not. To evaluate the efficacy of Egfl7 for early diagnosis and differential diagnosis among high risk populatin and HCC compared with AFP.Methods: We established a sandwich ELISA to detect serum Egfl7, based on murine monoclonal antibody and goat polycolonal antibody. The preotreative serum samples of 131 HCCs, 120 chronic liver disease patients including hepatitis, hepatofibrosis and portal hypertension, and 382 healthy donors are collected. Meanwhile, the clinical and pathological information of all the patients is gathered. Serum AFP and serum Egfl7 concentrations are detected differently for randomized double-blind trials.Results: The quality control of sandwich ELISA for serum Egfl7 shows intra-, interassay and interference coefficient of variation (CV) are <5%, >15% and <10%. Concertration of serum AFP and serum Egfl7 have statistic differences among HCC, chronic liver disease and healthy donors (135.56ng/mL vs. 12.30ng/mL vs. 1.52ng/mL, 3891.67ng/mL vs. 1600.28ng/mL vs. 1088.83ng/mL, P < 0.05). The best serum Egfl7 diagnostic threshold is 2620.00ng/mL and the diagnosit threshold of serum AFP is 20.00ng/mL. In serum Egfl7 single detection, the sensitivity in AFP negative HCC is 67.3%. For the diagnosis of HCC in normal population, sensitivity of Egfl7 is higher than that of AFP (74.8% vs. 60.3%, P < 0.05) , and its specificity is lower than that of AFP single test (81.2% vs. 96.9%, P<0.05) . AUCs have not stastatic diference between Egfl7 and AFP (0.840 vs. 0.881, P>0.05). Between HCC and chronic liver disease, the sensitivity, specificity and accuracy of serum Egfl7 are higher than those of serum AFP (74.8% vs. 60.3%, 71.7% vs. 58.3%, 73.3% vs. 59.4%, P < 0.05).Conclusion: Serum Egfl7 is firstly detected by the reliable sandwich ELISA. Serum Egfl7 single detection has higher sensitivity, but its specificity is lower than that of AFP single detection for diagnosis of HCC among normal population. It is very critical for the diagnosis of AFP negative HCC, which can make up for the short of serum AFP single detection. For screening and surveillance among high risk population, serum Egfl7 is good to improve the poor early and differential diagnosis. Above all, serum Egfl7 is a novel serological diagnositic marker for HCC.