Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas

Abstract

Hepatocellular carcinomas (HCCs) and bile duct carcinomas (BDCs) have a poor prognosis. Therefore, surveillance strategies including sensitive and specific serum markers for early detection are needed. Recently, Golgi Phosphoprotein 2 (GOLPH2) has been proposed as a serum marker for HCC, but GOLPH2 expression data in liver tissues was not available. Using tissue microarrays and immunohistochemistry, we semiquantitatively analyzed GOLPH2 protein expression in patients with HCC (n ‫؍‬ 170), benign liver tumors (n ‫؍‬ 22), BDC (n ‫؍‬ 114) and normal liver tissue (n ‫؍‬ 105). A newly designed sandwich enzyme-linked immunoassay (ELISA) was used to analyze GOLPH2 levels in the sera of patients with HCC (n ‫؍‬ 62), hepatitis C virus (HCV) (n ‫؍‬ 29), BDC (n ‫؍‬ 10), and healthy control persons (n ‫؍‬ 12). By immunohistochemistry 121/170 (71%) of HCC showed strong GOLPH2 expression, which was significantly associated with a higher tumor grade (P ‫؍‬ 0.01). A total of 97/114 (85%) BDCs showed a strong GOLPH2 expression which proved to be an independent prognostic factor for overall survival (P < 0.05). Serum levels of GOLPH2 measured by ELISA were significantly elevated in patients with HCC with underlying HCV infection (median 18 mg/L, P < 0.05) and patients with BDC (median ‫؍‬ 14.5 mg/L, P < 0.01) in comparison to healthy controls (median 4 mg/L). Conclusion: GOLPH2 protein is highly expressed in tissues of HCC and BDC. GOLPH2 protein levels are detectable and quantifiable in sera by ELISA. In patients with hepatitis C, serial ELISA measurements in the course of the disease appear to be a promising complementary serum marker in the surveillance of HCC. GOLPH2 should be further evaluated as a serum tumor marker in BDC on a larger scale.

Prognostic Value of Serum AFP, AFP-L3, and GP73 in Monitoring Short-term Treatment Response and Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

“…Elevated AFP-L3 levels were associated with larger tumor size, a later clinical stage, vascular invasion, poor tumor differentiation, and distant metastasis (Oka et al, 2001;Yoshida et al, 2002;Carr et al, 2007;Saito et al, 2012). Other research studies (Riener et al, 2009;Hu et al, 2010) observed that GP-73 levels were significantly higher in patients with hepatitis C-derived HCC and a high tumor grade. In our study, we evaluated tumor size, tumor number, and vascular invasion by imaging conducted before RFA and collected clinical information about hepatitis infection status, liver function, clinical stage, and other variables.…”

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

“…GOLPH2 expression is closely correlated with many diseases (Kim et al, 2012), including hepatocellular carcinoma (Riener et al, 2009), kidney cancer , prostate cancer Wei et al, 2008;Laxman et al, 2008;Roobol et al, 2011), seminoma (Fritzsche et al, 2010), lung adenocarcinoma (Zhang et al, 2010), and others. GOLPH expression was significantly higher in the urine of patients with prostate cancer than in normal controls (Laxman et al, 2008;Roobol et al, 2011), and both the mRNA and protein levels of GOLPH2 were significantly higher than in the normal controls.…”

“…GOLPH2 is a very important biomarker in a variety of diseases (Kim et al, 2012). GOLPH2 was detected in the lesions and sera of patients with liver disease (Riener et al, 2009), and in the lesions of patients with kidney cancer . Patients with prostate cancer also had significantly higher expression of GOLPH2 Wei et al, 2008).…”

Serum Golgi Phosphoprotein 2 level: A better marker than alpha-fetoprotein for diagnosing early hepatocellular carcinoma

“…We read with interest the article by Riener et al 1 reporting the potential usefulness of Golgi Phosphoprotein 2 (GOLPH2) as a new serum biomarker for diagnosing hepatocellular carcinoma (HCC). We would like to draw attention to similar studies on the use of serum GOLPH2 in the differentiation of HCC patients from controls with no liver disease and patients with cirrhosis.…”