Clinical proteomics for liver disease: a promising approach for discovery of novel biomarkers

Diagnostic methods for hepatocellular carcinoma (HCC) include imaging, such as abdominal ultrasonography and computed tomography (CT), and measurement of serum tumor markers. Alpha-fetoprotein (AFP), AFP lectin fraction L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP, also known as PIVKA-II) are widely used clinically as serum tumor markers of HCC. However, the sensitivity of AFP or DCP for detecting early stage HCC is only 30-60% [1-4]. Although combination measurements of AFP and DCP can improve the diagnostic performance, the diagnostic accuracy is still low for HCC lesions of ≤2 cm. Therefore, the development of a new diagnostic method for early stage HCC is needed to improve outcomes [5-7].The main cause of liver cirrhosis and HCC is persistent hepatitis B or C virus infection. The degree of hepatic fibrosis is associated with the occurrence of HCC, and serum hyaluronic acid and type IV collagen levels are used for diagnosis of hepatic fibrosis including cirrhosis, but these markers do not always reflect the stage of hepatic fibrosis assessed by liver biopsy [8,9]. In addition, the incidence of nonalcoholic fatty liver diseases (NAFLD) has increased worldwide, but no specific biomarker is available and invasive liver biopsy is still required for definite diagnosis of NAFLD, especially for nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and HCC [10,11]. Therefore, there is a need to identify blood (serum or plasma) markers that are specific for early diagnosis of HCC, prediction of carcinogenesis from liver cirrhosis, progression of liver cirrhosis, and diagnosis of NASH. These analyses may also aid in the elucidation of the mechanism(s) underlying the pathogenesis of hepatitis and hepatocarcinogenesis.Proteomics is the term used for exhaustive analysis of protein structure and function in an organ or tissue. The levels of gene expression and protein production are not necessarily proportional, and protein activity is frequently regulate