Abstract
BackgroundEpidermal 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 the diagnosis of early HCC remains unknown. In this study, we therefore evaluate the efficacy of serum Egfl7 for early HCC diagnosis and compare it with alpha-fetoprotein (AFP).MethodsSerum Egfl7 levels in testing cohort (1081 participants) and validation cohort (476 participants) were measured by a sandwich enzyme-linked immunoassay (ELISA). The cut-off value of Egfl7 was determined by Youden’s index and the efficacies of Egfl7 and AFP in diagnosing early HCC were estimated by receiver operating characteristic (ROC).ResultsSerum Egfl7 was significantly elevated in patients with early HCC than all non-HCC controls in whatever Testing Cohort or Validation Cohort. In the Testing Cohort, ROC curves showed the optimum cut-off value of Egfl7 was 2610 ng/mL and Egfl7 showed a significantly higher sensitivity than AFP in discriminating early HCC from healthy individuals (77.4% vs. 65.3%, P = 0.0013) but the area under ROC (AUROC) and accuracy of Egfl7 and AFP were similar (0.860 vs. 0.868, P = 0.704; 80.2% vs. 83.8%, P = 0.184). In distinguishing patients with early HCC from patients with chronic liver disease (CLD), the AUROC, sensitivity, specificity and accuracy of Egfl7 were 0.800, 75.2, 71.7 and 73.5%, which were all significantly higher than AFP (0.675, 61.8, 62.0 and 61.9% in order). Egfl7 also showed a significant higher sensitivity and accuracy than AFP (76.6% vs. 64.0%, P = 0.0031; 79.9% vs. 66.1%, P < 0.0001) in differentiating early HCC patients from non-HCC individuals. 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.ConclusionEgfl7 is a valuable serum marker in the diagnosis of early HCC and could complement the efficacy of AFP, especially in distinguishing early HCC from CLD and identifying patients with AFP-negative early HCC.
Highlights
Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with Hepatocellular carcinoma (HCC) by our previous studies
The median serum level of Egfl7 in early HCC was 4017.28 ng/mL, and it was significantly higher than metastatic liver cancer (2707.6 ng/mL; 95% Confidence interval (CI), 274.2–5234.8 ng/mL; P = 0.0056), benign liver tumors (1756.6 ng/mL; 95% CI, 494.8–3343.8 ng/mL; P = 0.0023), chronic liver disease (1600.3 ng/mL; 95% CI, 20.4–6232.1 ng/mL; P < 0.0001) and healthy individuals (1082.80 ng/mL; 95% CI, 7.5–4906.1 ng/mL; P < 0.0001)
There was no significant difference between the groups of benign liver tumors and chronic liver disease (P = 0.7825), the serum Egfl7 levels in these two groups were higher than the healthy individuals (P = 0.0138 and P = 0.0161, respectively)
Summary
Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with HCC by our previous studies. We evaluate the efficacy of serum Egfl for early HCC diagnosis and compare it with alpha-fetoprotein (AFP). Despite the great improvements in treatments, the long-term survival of patients with HCC remains unsatisfactory, with a 5-year survival rate of less than 20%, mainly due to limited effective therapeutic options for HCC patients with late stage [5]. The early detection of HCC, providing the opportunity for radical treatment, is crucial to reduce the mortality and improve the long-term prognosis of this lethal malignancy [6]. The sensitivity of AFP in the early detection of HCC is only 39 to 65%, which means that its false-negative rate is 35 to 61% [12,13,14]
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