A comparative evaluation of Golgi protein-73, fucosylated hemopexin, α-fetoprotein, and PIVKA-II in the serum of patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma

Morota, Kaori; Nakagawa, Masatoshi; Sekiya, Rika; Hemken, Philip M.; Sokoll, Lori J.; Elliott, Debra J.; Chan, Daniel W.; Dowell, Barry L.

doi:10.1515/cclm.2011.097

Cited by 59 publications

(44 citation statements)

References 26 publications

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“…Similar reports have been made for our fourth validation marker; hemopexin. A study, which measured levels of fucosylated HPX found significantly, elevated quantities of its expression in a cohort of 229 serum samples from patients with chronic hepatitis, LC, and HCC [53]; a finding that was previously reported in an earlier publication [54]. A recent study by Japanese investigators also assessing the clinical utility of serum fucosylated hemopexin in HCC, LC and chronic hepatitis subjects concluded that the glycoprotein could be used as a biomarker potentially indicative of a hypercarcinogenic liver [55].…”

Section: Discussionmentioning

confidence: 99%

Protein Profiling in Hepatocellular Carcinoma by Label-Free Quantitative Proteomics in Two West African Populations

et al. 2013

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BackgroundHepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC.MethodsMass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis.ResultsTwenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages.ConclusionsThe validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance.

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Section: Discussionmentioning

confidence: 99%

Protein Profiling in Hepatocellular Carcinoma by Label-Free Quantitative Proteomics in Two West African Populations

et al. 2013

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“…In recent years, in addition to AFP, new biomarkers possessing fucosides have been discovered. For example, Golgi protein 73 (GP73) content in the blood of patients with HCC was found to be elevated, and the protein was ␣1-6-hyperfucosylated (43)(44)(45)(46). In addition, patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan containing outer arm (␣1-3)-fucosylation in ␣-antitrypsin in the blood, but increases in core (␣1-6)-fucosylation were observed only on ␣1-antitrypsin from patients with liver cancer (47).…”

Section: Discussionmentioning

confidence: 99%

A Novel Core Fucose-specific Lectin from the Mushroom Pholiota squarrosa

Kobayashi

Tateno

Dohra

et al. 2012

Journal of Biological Chemistry

109

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Background: Fuc-␣1-6 oligosaccharide has a variety of biological functions. Results: Purification of a novel Fuc␣ 1-6-specific lectin from the mushroom Pholiota squarrosa. Conclusion: The lectin binds only to core ␣1-6-fucosylated N-glycans and not to the other types of fucosylated oligosaccharides. Significance: The lectin will be a promising tool for analyzing the biological functions of ␣1-6 fucosylation.

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“…Recently, serum GP73 has been reported as a potential marker for diagnosing HCC [12–16]. However, some studies showed that serum levels of GP73 in HCC patients were markedly overlapped with [13, 17, 18] or even lower than those in cirrhotic patients [19, 20]. This may compromise its diagnostic accuracy because most HCC cases develop from cirrhosis [21–23].…”

Section: Introductionmentioning

confidence: 99%

Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma

et al. 2017

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Golgi protein 73 (GP73) has been suggested as a serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, this has been challenged in recent years. In the present study, we found that the serum GP73 increased in HCC patients with cirrhosis but not in those without cirrhosis. The receiver operating characteristic curve (ROC) analysis demonstrated that serum GP73 had poor performance for differentiating HCC patients from cirrhosis patients. In addition, the immunohistochemistry revealed that aberrant expression of GP73 was primarily observed in cirrhotic and tumor liver tissues from both cirrhosis and HCC patients, but rarely in non-cirrhotic liver tissues from HCC patients without cirrhosis. Moreover, serum Alpha-fetoprotein in HCC patients with cirrhosis decreased sharply after resection of tumor tissue, while the serum GP73 remained stable. These data indicated that the background of cirrhosis was related to the elevation of serum GP73 in HCC patients. In conclusion, serum GP73 is not a suitable diagnostic marker for HCC.

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A comparative evaluation of Golgi protein-73, fucosylated hemopexin, α-fetoprotein, and PIVKA-II in the serum of patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma

Abstract: PIVKA-II showed superior sensitivity and specificity for HCC compared with the other three markers. GP73 may be useful for detecting cirrhosis as a risk factor for HCC. Fuc-HPX showed inferior sensitivity and specificity compared to the other markers.

Cited by 59 publications

References 26 publications

Protein Profiling in Hepatocellular Carcinoma by Label-Free Quantitative Proteomics in Two West African Populations

Protein Profiling in Hepatocellular Carcinoma by Label-Free Quantitative Proteomics in Two West African Populations

A Novel Core Fucose-specific Lectin from the Mushroom Pholiota squarrosa

Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma

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