Aveneu Park, Starling, Australia

GOLM1 is a type II Golgi membrane protein

GOLM1 is a type II Golgi membrane protein which contains a short N-terminal sequence in the cytoplasm, and its expression is elevated by viral infection (1). Previous studies, by comparing the gene expression profiles of hepatocellular carcinoma (HCCs) with and without extra-hepatic metastasis, showed that GOLM1 by regulation of EGFR/RTK recycling may promote HCC, suggesting therapeutic targeting of GOLM1 as a potential strategy for fighting against HCC metastasis (2,3).

CCL25 acts through different pathways including Akt signaling and pigment epithelium-derived factor (PEDF) induced signaling. In patients with primary sclerosing cholangitis (PSC), it was demonstrated that CCL25 activates ?4?7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium and consequently recruits CCR9+ T cells (originally activated in the gut) to the liver (4).

ICAM1 gene encodes a cell surface glycoprotein typically expressed on endothelial and the immune system cells. Patients with primary biliary cirrhosis (PBC), PSC and chronic active hepatitis (autoimmune) were found to have significant increases in expression of ICAM-1 compared with normal healthy subjects (2). Increased serum concentrations of ICAM-1 have been found in intra- and in extrahepatic cholestasis. Additionally, ICAM-1 have been detected in the bile which rise the hypothesis of removal of ICAM-1 through the bile. Therefore, high concentration of ICAM-1 whether elevated synthesis or reduced elimination can cause increased ICAM-1 serum levels in patients with cholestatic liver diseases (5). High levels of ICAM-1 was also observed in patients with autoimmune hepatitis (AICH) (6).

MGST3 encodes a member of the membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) protein family. MGST3 shows glutathione-dependent peroxidase activity towards lipid hydroperoxides. It was shown that reactive oxygen species (ROS) such as the superoxide anion and the hydroxyl radical ROS generated by inflammatory processes and possibly by endotoxin or bile acids play a pivotal role in progression of PBC and also in a variety of human liver disorders, including chronic viral hepatitis, alcoholic liver disease, Wilson’s disease and haemachromatosis (7). In our current study, we assessed the hypothesise that PBC patients unresponsive to obeticholic acid (OCA) have differential SNP profile, gene expression, cytokine responses and/or human betaretrovirus levels accounting for the differential response to treatment. The results found MGST3 to be downregulated in the responders and is, therefore, possibly a candidate risk gene and prognosis gene.

LAMA4, a family of extracellular matrix glycoproteins, is one of the major noncollagenous constituent of basement membranes. Examining the expression level of LAMA4 in patients with hepatocellular carcinoma showed that LAMA4 was up-regulated on both mRNA and protein levels in the patients. In addition, elevated expression level of LAMA4 was intensely connected with tumor progression and metastasis, suggesting LAMA4 as a potential novel marker for diagnosis of tumor invasion and metastasis (8).

FYN gene, a member of the protein-tyrosine kinase oncogene family, is involved in the cell growth regulation. It was found that FYN along with YWHAZ genes are key factors in the liver metastases of uveal melanoma patients and play pivotal roles in proliferation, suggesting the hypothesis of  the higher incidence of metastases in uveal melanoma (9). In addition, it was shown that the cellular Csk kinase through controling the activity of FYN, which is known to directly interact with the NS5A protein of hepatitis C virus (HCV), is playing crucial role in HCV replication (10).