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. 2018 Aug;97(35):e11781.
doi: 10.1097/MD.0000000000011781.

High level of serum Cripto-1 in hepatocellular carcinoma, especially with hepatitis B virus infection

Yingyu Zhang  1 , Hongqin Xu, Xiumei Chi, Yuxiang Fan, Ying Shi, Junqi Niu
Affiliations

High level of serum Cripto-1 in hepatocellular carcinoma, especially with hepatitis B virus infection

Yingyu Zhang et al. Medicine (Baltimore). 2018 Aug.

Abstract

Background: Human Cripto-1 (CR-1), a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic protein family (EGF-CFC), is highly expressed in a variety of human cancers. We aimed to detect serum CR-1 level in liver diseases especially in hepatocellular carcinoma (HCC) patients.

Methods: Serum CR-1 level was Sandwich-type enzyme-linked immuno sorbent assay (ELISA) detected in 330 patients with liver diseases including HCC, cirrhosis, and chronic hepatitis and 50 volunteers without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as control.

Results: The serum CR-1 level was significantly higher in HCC patients than volunteer controls and it was also significantly higher in HBV-related HCC than HCV-related HCC. In addition, serum CR-1 level was correlated with serum alpha-feto-protein (AFP) in HBV-related HCC patients. The serum CR-1 was also higher in cirrhosis and chronic hepatitis than volunteer controls. The serum CR-1 in HBV-related cirrhosis was higher than chronic hepatitis B, but there was no significant difference between HCV-related cirrhosis and chronic hepatitis C.

Conclusions: Serum CR-1 was higher in HCC patients and might serve as a complementary biomarker to clinical diagnosis of HBV-related HCC. The high level of serum CR-1 in HBV-related liver disease might be partly attributed to HBV infection.

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Conflict of interest statement

The authors report no conflict of interest.

Figures

Figure 1
Figure 1
Serum CR-1 level detected by sandwich ELISA in volunteer controls (n = 50), HBV-related HCC (n = 74), HCV related HCC (n = 34), HCC without HBV or HCV infection (n = 7), and metastatic hepatic carcinoma (n = 10). The serum CR-1 levels in HBV-related HCC, HCV related HCC, and HCC without HBV or HCV infection group showed significant differences with volunteer (both P < .05). CR-1 = cripto-1, ELISA = enzyme-linked immuno sorbent assay, HBV = hepatitis B virus, HCC = hepatocellular carcinoma, and HCV = hepatitis C virus.
Figure 2
Figure 2
Serum CR-1 level detected by sandwich ELISA in HBV-related liver cirrhosis (n = 77) and chronic HBV infection (n = 62). Serum CR-1 level in HBV-related liver cirrhosis was significantly higher than chronic HBV infection (P < .05). But serum CR-1 level had no statistically difference between HBV-related liver cirrhosis with HBV-related HCC (P = .756). CR-1 = cripto-1, ELISA = enzyme-linked immuno sorbent assay, HBV = hepatitis B virus, and HCC = hepatocellular carcinoma.
Figure 3
Figure 3
Serum CR-1 level detected by sandwich ELISA in HCV related liver cirrhosis (n = 32) and chronic hepatitis C (n = 34). Serum CR-1 level in HCV related cirrhosis was not significantly different from that in chronic hepatitis C and HCV related HCC (P = .509 and P = .801, respectively). CR-1 = cripto-1, ELISA = enzyme-linked immuno sorbent assay, HCC = hepatocellular carcinoma, and HCV = hepatitis C virus.
Figure 4
Figure 4
ROC curves for CR-1 in differentiating the HBV-related HCC and control group. The area under the curve was 0.623. The sensitivity and specificity at the cutoff value of 714.20 pg/mL were 33.80% and 91.50%, respectively. ROC curves = receiver operating characteristics curves, CR-1 = cripto-1, HBV = hepatitis B virus, and HCC = hepatocellular carcinoma.
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