Clinical Utility of Alpha Fetoprotein and HCCR-1, Alone or in Combination, in Patients with Chronic Hepatitis, Liver Cirrhosis and Hepatocellular Carcinoma

Abstract

Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma (HCC). However, it has been indicated that HCCR-1 (human cervical cancer oncogene 1) might be supplementary to AFP in the detection. We conducted a prospective study in 120 normal and 524 liver disease patients to evaluate the significance of simultaneous measurement of 2 tumor markers (AFP and HCCR-1) in the diagnosis of HCC through the cohort study in Korea and China. We also performed immunohistochemical studies using 25 normal subjects (N), 32 liver cirrhosis (LC) and 116 HCC tissues. The sensitivities of AFP (20 ng/mL) and HCCR-1 (10 ng/mL) in HCC were 55.8% (164/294) and 44.2% (130/294), respectively. When AFP was combined with HCCR-1, sensitivities increased to 4.2% (N), 12.7% (chronic hepatitis; CH), 50.0% (LC), and 77.2% (HCC), respectively. Although there was no significant difference in the diagnostic rate for HCC between AFP and HCCR-1, many cases for AFP-negative HCC were positive for HCCR-1 and vice versa. Moreover, the combined use of AFP and HCCR-1 improved the diagnostic rate to 70.8% in small HCC (< 2 cm) and 81.6% in large HCC (≥ 2 cm), respectively. AFP and HCCR-1 are independent markers. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

“…Serum HCCR was positive in 76.9% (40 of 52) ANHC patients ( 147 ); in addition, nine patients with metastatic lesions who were negative for AFP were positive for HCCR. However, another study showed that HCCR-1 has a positive rate of only 48.5% (63 of 130) in ANHC ( 148 ). In a multicenter prospective study ( 5 ), HCCR-1 levels did not significantly correlate with HCC clinicopathological characteristics such as age, gender, tumor size, and lymph node metastasis, but positively correlated with histological grading.…”

Up-regulation of human cervical cancer proto-oncogene contributes to hepatitis B virus-induced malignant transformation of hepatocyte by down-regulating E-cadherin

“…Several studies indicate that HCCR expression increases as liver cells gradually progress from LC to HCC [ 5 ]; thus, HCCR expression may be a useful marker for HCC progression and/or prognosis [ 3 ]. We have made similar observations in clinical samples.…”

“…HCC is now the most common cancer in rural areas of China and the second most common in urban areas [ 2 ]. Recent research has supported that human cervical cancer proto-oncogene (HCCR) is a specific and sensitive biomarker independent of serum alpha-fetoprotein (AFP) for the diagnosis of HCC [ 3 – 5 ]. Several studies report that normal liver tissues show minimal, or no, HCCR expression, whereas expression is much higher in individuals with chronic hepatitis, liver cirrhosis (LC), or small and large HCC [ 5 , 6 ].…”

Analysis of serum α-fetoprotein-L3% and des-γ carboxyprothrombin markers in cases with misleading hepatocellular carcinoma total α-fetoprotein levels

“…Their combined use appears to increase the accuracy and sensitivity of serological diagnosis of HCC (24)(25)(26)(27)(28)(29)(30). AFP-L3% and DCP are HCC markers that can be measured on the same platform, making testing more friendly to clinical laboratories.…”