Golgi protein 73 and its diagnostic value in liver diseases

Abstract

Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis-Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non-viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings.

Keywords: GP73; hepatitis; liver cancer; liver cirrhosis.

Figure 1

A, GP73 expression levels in hepatocytes in the course of acute and chronic liver disease. Normal hepatocyte GP73 expression is minimal. Marked and reversible increases in the percentage of GP73‐positive hepatocytes, and their cellular GP73 levels occur in acute hepatitis. Progressive up‐regulation is also observed in chronic liver disease and can be reversed by treatment of underlying disease aetiology (ie, steroid treatment of autoimmune hepatitis) and resolution of chronic hepatitis. GP73 expression in hepatocellular cancer cells is further increased (2‐ to 3‐fold) in comparison with patients with cirrhosis. B, Structural features of GP73 and sGP73. GP73 consists of a short cytoplasmic N‐terminus with a myristoylation domain followed by a single TM and large C‐terminal ectodomain. The N‐terminus contains two coiled‐coil domains and is N‐glycosylated. The C‐terminus is highly acidic of unknown function. Furin cleavage after aa 55 results in the extracellular release of sGP73. aa, amino acid; ELISA, enzyme‐linked immunosorbent assay; GP73, Golgi protein 73; HCC, hepatocellular carcinoma; sGP73, serum form of Golgi protein 73; TM, transmembrane domain103

Figure 2

Immunoblot analysis of GP73 levels in controls, cirrhosis and hepatocellular carcinoma (HCC). The top panel shows immunoblot analyses of sera from controls without liver disease, the middle panel from cirrhosis and lower panel from subjects with HCC 184

Figure 3

The proposed mechanism for BTC assay185

Figure 4

Serum Golgi protein 73 (GP73) is increased in patients with hepatocellular carcinoma (HCC), with higher sensitivity and specificity than alpha‐fetoprotein (AFP). A, The GP73 values for HCC‐related diseases. The serum GP73 level for healthy subjects, patients with cirrhosis and patients with HCC was 1.2 (0.9e1.7) relative units (RU), 4.7 (2.6e8.0) RU and 14.7 (8.4e29.4) RU, respectively. ^§ P < 0.001 vs HCC and cirrhosis. B, The receiver operating characteristic (ROC) curve for combined AFP and GP73 in HCC diagnosis of all subjects. The points in the ROC curve indicate different GP73 values with corresponding sensitivity and specificity, from which the cut‐off value was chosen, and 8.5 RU (boxed) was the cut‐off value for GP73186