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      Evaluation of α-fetoprotein-L3 and Golgi protein 73 detection in diagnosis of hepatocellular carcinoma

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          Abstract

          Aim of the study

          Hepatocellular carcinoma (HCC) is common throughout the world. Most HCCs are diagnosed at an advanced stage. There is an urgent need to find new methods for screening and surveillance of individuals at risk for HCC. The aim of this study was to evaluate serum α-fetoprotein (AFP)-L3 and serum Golgi protein 73 (GP73) detection in diagnosis of HCC with different AFP concentration.

          Material and methods

          One hundred and eighty one patients were involved, including 102 with HCC and 79 with benign liver disease. The serum AFP-L3 and GP73 was measured by a liquid-phase binding assay and quantitative enzyme-linked immunosorbent assay, respectively.

          Results

          Of the 102 HCC patients, 53 were positive for AFP, 77 were positive for AFP-L3, and 79 were positive for GP73. The maximum area under the curve for AFP-L3% and for GP73 was significantly different from the AUC of 0.5525 for total AFP ( p < 0.01). AFP-L3% was not detected for AFP < 20 ng/ml. However, elevated GP73 was detected in 87.50% of the patients. In the HCC patients with total AFP 20–400 ng/ml, elevated AFP-L3 was detected in 26 patients, whereas in 23 patients elevated GP73 could be detected. In the HCC patients with a total AFP > 400 ng/ml, AFP-L3% > 10% was present in 96.23%, and GP73 was detected in 87.50%.

          Conclusions

          The determination of AFP-L3% and GP73 in combination with AFP can increase the sensitivity and specificity in diagnosis of HCC. α-fetoprotein-L3% and GP73, in combination with AFP, are useful biomarkers to confirm the diagnosis of HCC.

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          Most cited references16

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          GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma.

          Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC). The aims of this study were to determine if GP73 is detected in the serum, and to establish the sensitivity and specificity of serum GP73 for diagnosing HCC. Serum GP73 was detected by immunoblots and quantified by densitometric analysis. A total of 352 patients were studied. Serum GP73 levels were significantly higher in patients with HCC compared to those with cirrhosis (P < 0.001). GP73 had a sensitivity of 69% and a specificity of 75% at the optimal cutoff point of 10 relative units, with an area under the receiver operating curve of 0.79 vs. 0.61 for AFP (P = 0.001). GP73 levels had significantly higher sensitivity (62%) than AFP (25%) for diagnosing early HCC (P < 0.0001). Moreover, GP73 levels were elevated in the serum of 57% (32/56) of individuals with HCC who had serum AFP levels less than 20ng/ml. Higher levels of GP73 can be found in the serum of patients with HCC than of those without. GP73 was better than AFP for the diagnosis of early HCC. Further validation studies are needed to confirm the role of GP73 in the early detection of HCC.
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            Molecular viral oncology of hepatocellular carcinoma.

            Hepatocellular carcinoma (HCC) is the fifth most common cancer, but the third leading cause of cancer death, in the world, with more than 500,000 fatalities annually. The major etiology of HCC/liver cancer in people is hepatitis B virus (HBV), followed by hepatitis C virus infection (HCV), although nonviral causes also play a role in a minority of cases. Recent molecular studies confirm what was suspected: that HCC tissue from different individuals have many phenotypic differences. However, there are clearly features that unify HCC occurring in a background of viral hepatitis B and C. HCC due to HBV and HCV may be an indirect result of enhanced hepatocyte turnover that occurs in an effort to replace infected cells that have been immunologically attacked. Viral functions may also play a more direct role in mediating oncogenesis. This review considers the molecular and cellular mechanisms involved in primary hepatocellular carcinoma, using a viral perspective.
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              Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein.

              The sugar-chain structures of circulating alpha-fetoprotein in patients with hepatocellular carcinomas differ from those in patients with cirrhosis. We studied the reactivity of alpha-fetoprotein with two lectins, Lens culinaris agglutinin A and erythroagglutinating phytohemagglutinin, to monitor the evolution of hepatocellular carcinoma in patients with cirrhosis. Among 361 patients with cirrhosis caused mainly by chronic hepatitis B or hepatitis C virus infection, 33 with base-line serum alpha-fetoprotein concentrations > or = 30 ng per milliliter or more were found to have hepatocellular carcinomas during a mean follow-up of 35 months. The lectin-reactive profiles of the alpha-fetoprotein in the serum of these 33 patients were analyzed and compared with those in the serum of 32 patients with cirrhosis who had increased base-line serum alpha-fetoprotein concentrations and were followed for at least 24 months but in whom hepatocellular carcinoma did not develop. At the time of tumor detection, 24 (73 percent) of the 33 patients with cirrhosis and hepatocellular carcinoma had higher percentages of L. culinaris agglutinin A-reactive alpha-fetoprotein (alpha-fetoprotein L3), erythroagglutinating phytohemagglutinin-reactive alpha-fetoprotein (alpha-fetoprotein P4+P5), or both than the 32 patients with cirrhosis but no hepatocellular carcinoma. Among the 24 patients, one or both of the markers were first elevated 3 to 18 months before the hepatocellular carcinoma was detected by imaging techniques. Measurements of the alpha-fetoprotein L3 and alpha-fetoprotein P4+P5 fractions of serum alpha-fetoprotein allow the differentiation of hepatocellular carcinoma from cirrhosis in some cases and serve as predictive markers for the development of hepatocellular carcinoma during the follow-up of patients with cirrhosis.
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                Author and article information

                Journal
                Contemp Oncol (Pozn)
                Contemp Oncol (Pozn)
                WO
                Contemporary Oncology
                Termedia Publishing House
                1428-2526
                1897-4309
                18 June 2014
                2014
                : 18
                : 3
                : 192-196
                Affiliations
                Department of Oncology, General Hospital of Beijing Command of PLA, Beijing, PR China
                Author notes
                Address for correspondence: Mancang Zhao, Department of Oncology, General Hospital of Beijing Command of PLA, No. 28 Fuxing Road Haidian District, Beijing 100700, China. e-mail: jzwlcn@ 123456126.com
                Article
                22866
                10.5114/wo.2014.43157
                4268990
                25520580
                6521328e-5b62-4ef5-9206-8ef5668b42e1
                Copyright © 2014 Termedia

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 January 2013
                : 19 March 2013
                : 29 August 2013
                Categories
                Original Paper

                α-fetoprotein,lectin,reactive α,fetoprotein,hepatocellular carcinoma

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