Serum Epidermal Growth Factor-like domain 7 Serves as a Novel Diagnostic Marker for Early Hepatocellular Carcinoma

Background: Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with HCC by our previous studies. However, its efficacy in diagnosis of early HCC remains unknown. In this study we evaluate the efficacy of serum Egfl7 for early HCC diagnosis and compare it with alpha-fetoprotein (AFP). Methods: Serum Egfl7 levels in testing cohort (1065 participants) and validation cohort (464 participants) were measured by a sandwich enzyme-linked immunoassay (ELISA). The efficacies of Egfl7 and AFP in diagnosing early HCC were estimated by receiver operating characteristic (ROC). Results: Serum Egfl7 was significantly elevated in patients with early HCC than all non-HCC controls. At the cut-off value of 2610 ng/mL, the area under ROC, sensitivity, specificity and accuracy of Egfl7 were 0.800, 75.2 %, 71.7% and 73.5% in discriminating early HCC from chronic liver disease (CLD), compared with 0.675, 61.8%, 62.0% and 61.9% for AFP using 20 ng/mL as a cut-off value. Egfl7 also exhibited a significant higher sensitivity and accuracy than AFP in differentiating early HCC patients from non-HCC individuals including healthy individuals and patients with CLD (76.6% vs. 64.0%, 79.9% vs. 66.1%). Additionally, 70.8% of early HCC patients with negative AFP could be diagnosed by Egfl7 and the combined use of Egfl7 and AFP increased the sensitivity to 91.0%. These results were confirmed by a validation cohort. Conclusion: Egfl7 is a valuable serum marker in early diagnosis of HCC with a better sensitivity and accuracy than AFP.