Increased Golgi protein 73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival

Sun, Yongliang; Yang, Huayu; Mao, Yilei; Xu, Haifeng; Zhang, Jinchun; Li, Guangbing; Lu, Xin; Sang, Xinting; Zhao, Haitao; Zhong, Shouxian; Huang, Jiefu; Zhang, Hongbing

doi:10.1111/j.1440-1746.2011.06733.x

Cited by 57 publications

(65 citation statements)

References 19 publications

(54 reference statements)

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“…In a previous Chinese study, a significant correlation was identified between the overexpression of GP73 at the protein and/or mRNA levels and the aggressive behavior of HCC. However, no correlation was reported with the overall patient survival rates (22). In addition, Mao et al identified that GP73 may also be utilized for the surveillance of HCC recurrence in post-operative patients (17).…”

Section: Discussionmentioning

confidence: 99%

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Hou

Xiao

et al. 2013

Oncology Letters

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Golgi protein 73 (GP73) is a resident Golgi type II transmembrane protein that has been reported to markedly increase in chronic liver disease, particularly in hepatocellular carcinoma (HCC). However, it remains unclear as to whether serum GP73 represents a reliable serum marker for the diagnosis of HCC. The aim of the present study was to evaluate the diagnostic value of serum GP73 in patients with HCC and to determine the diagnostic accuracy of measuring serum GP73 in combination with α-fetoprotein (AFP) and γ-glutamyl transferase isoenzyme II (GGT-II) in HCC. Serum GP73 was detected using a time-resolved fluorescence immunological assay (TRFIA) and enzyme-linked immunosorbent assay (ELISA) in 79 HCC cases, including 16 liver cirrhosis, 30 chronic hepatitis and 28 healthy individuals. The correlation between serum GP73 and tumor size and HCC grading was analyzed and the complementary diagnostic value of serum GP73, AFP and GGT-II was evaluated. TRFIA was established for the detection of serum GP73 and was sensitive and reproducible. The expression levels of serum GP73 were markedly higher in the patients with HCC when compared with those of the individuals with liver cirrhosis and chronic hepatitis or the healthy individuals. According to the receiver operating characteristic (ROC) curve, diagnostic sensitivity and specificity for HCC with a cut-off value of 78.1 ng/l were 73.4 and 79.0%, respectively. However, no correlation was identified among serum GP73 and tumor size or grading, and no correlations were identified among serum GP73, AFP and GGT-II. The diagnostic sensitivities for HCC, as detected by TRFIA of GP73, AFP and GGT-II, were 73.4, 55.6 and 68.4%, respectively, and the specificities were 80.0, 86.7 and 97.1%, respectively. The combined determination of these markers increased the diagnostic sensitivity to 96.3% for HCC. TRFIA functions as a sensitive and replicable assay for the detection of serum GP73. The levels of serum GP73 were significantly higher in the HCC group when compared with the individuals with benign liver diseases. Serum GP73 may serve as a potential independent diagnostic candidate for HCC and the combined determination of serum GP73, AFP and GGT-II may increase the diagnostic efficiency of HCC.

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Section: Discussionmentioning

confidence: 99%

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Hou

Xiao

et al. 2013

Oncology Letters

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“…One of the proteins identified in the serum of woodchucks with cancer and subsequently in the serum of people with HCC was golgi-proteins 73 (GP73). This protein has subsequently been analyzed in over 10,000 individuals with liver disease(Block et al, 2005b; Gu et al, 2009; Hann et al, 2010; Hu et al, 2010; Iftikhar et al, 2004; Jiang and Zhou, 2012; Liu et al, 2011; Maitra and Thuluvath, 2004; Malaguarnera et al, 2010; Mao et al, 2010; Mao et al, 2008; Marrero et al, 2005; Morota et al, 2011a; Ozkan et al, 2011; Riener, 2011; Riener et al, 2009; Schwegler et al, 2005; Shi et al, 2011; Sun et al, 2011; Tan, 2007; Tan et al, 2009; Tian et al, 2011; Wang et al, 2011a; Wang et al, 2009b; Wang et al, 2011b; Xu et al, 2011; Yamamoto et al, 2010; Zhao et al, 2010; Zhou et al, 2012) and for the most part, shown improved performance in the detection of HCC as compared to AFP. However, in several studies, GP73 either was either not elevated in HCC versus cirrhosis (Morota et al, 2011a; Riener et al, 2009) or was no better than AFP at differentiating HCC from cirrhosis.…”

Section: Glycomic Methodologies For the Identification Of Biomarkers mentioning

confidence: 99%

Glycosylation and Liver Cancer

Mehta

Herrera

Block

2015

Advances in Cancer Research

117

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Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development.

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“…In a study aimed to investigate the expression of GOLPH2 and its correlation with clinical parameters, significant overexpression of GOLPH2 at either protein- or mRNA-levels or both were fund to be associated with aggressive behavior of HCC, but not overall patient survival [19]. This observation suggests that GOLPH2 is not merely a marker of HCC progression but it may have HCC-promoting activities.…”

Section: Golph2 In Liver Diseasesmentioning

confidence: 99%

Golgi phosphoprotein 2 in physiology and in diseases

Kim

Zhang

et al. 2012

Cell Biosci

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Golgi phosphoprotein 2 (GOLPH2, also termed GP73 and GOLM1) is a type II transmembrane protein residing in the cis and medial-Golgi cisternae. GOLPH2 is predominantly expressed in the epithelial cells of many human tissues. Under poorly defined circumstances, GOLPH2 can be cleaved and released to the extracellular space. Despite of its relatively “young age” since the first description in 2000, the physiological and pathological roles of GOLPH2 have been the subject that has attracted considerable amount of attention in recent years. Here, we review the history of GOLPH2’s discovery and the multitude of studies by many groups around the world aimed at understanding its molecular, cellular, physiological, and pathogenic activities in various settings.

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Increased Golgi protein 73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival

Abstract: Significant overexpression of GP73 at both protein and mRNA levels along with overexpression of GP73 protein is associated with aggressive behavior of HCC, but not overall patient survival. Further research is needed to determine the potential of GP73 as a therapeutic target.

Cited by 57 publications

References 19 publications

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Glycosylation and Liver Cancer

Golgi phosphoprotein 2 in physiology and in diseases

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