Diagnostic value of the hemopexin N-glycan profile in hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common and rapidly fatal cancer. Current diagnostic methods for HCC have poor sensitivity and specificity, are invasive, and carry risk for complications. Newer markers are needed to overcome these problems and allow diagnosis of HCC at an earlier stage. In view of known associations between glycosylation changes and liver disease, we focused on the serum glycoprotein hemopexin and the specific characteristics of this liver-synthesized glycoprotein. METHODS: We studied 49 healthy volunteers and 81 patients divided into the categories of fibrosis, cirrhosis, and HCC with cirrhosis. Hemopexin was purified from study participants' serum by use of heme agarose beads. The hemopexin N-glycan profile was determined by use of the DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis technique. RESULTS: We found that branching alpha-1,3-fucosylated multiantennary glycans on hemopexin were increased in the HCC group compared with the cirrhosis without HCC, fibrosis, and healthy volunteer groups, whereas nonmodified biantennary glycans decreased progressively across groups from fibrosis to the cirrhosis and HCC groups. Summarization of this information in a new marker, called the hemopexin glycan marker, enabled distinction of patients with HCC and cirrhosis from healthy volunteers and patients with fibrosis or cirrhosis with a sensitivity and specificity of 79% and 93%, respectively. CONCLUSIONS: This study demonstrated hemopexin to be a model protein for studying liver-specific N-glycosylation. The hemopexin glycan marker could be a valuable complementary test to alpha-fetoprotein measurements for detection of HCC in patients with cirrhosis. Additional study of its utility for diagnosis and follow-up is recommended.

Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications.

Hepatocellular carcinoma is the 5th most common cancer in the world. Prognosis for this disease is poor since hepatocellular carcinoma is mostly diagnosed at an advanced stage. Serum alpha-fetoprotein (AFP) is one of the most common diagnostic markers for hepatocellular carcinoma. However, its diagnostic value is more and more questioned. Therefore, research has focussed on AFP related parameters (AFP mRNA and AFP glycoforms). The aim of this paper is to review the present knowledge on AFP and its related parameters in diagnosing and monitoring HCC. AFP related parameters can be arranged in two types: AFP mRNA and AFP glycoforms. AFP mRNA is a potentially prognostic marker and AFP mRNA assays are based on PCR techniques. The AFP glycoforms have diagnostic potential and assays are based on isoelectric focussing and lectin affinity electrophoretic methods. Up to now the diagnostic use of the AFP related parameters is limited. Although some of them are recommended as a complementary test, they cannot (yet) replace serum AFP as the golden standard of diagnostic markers for hepatocellular carcinoma.