Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma

Sterling, Richard K.; Jeffers, Lennox J.; Gordon, Fredric D.; Venook, Alan P.; Reddy, K. Rajender; Satomura, Shinji; Kanke, Futoshi; Schwartz, Myron; Sherman, Morris

doi:10.1016/j.cgh.2008.08.041

Cited by 120 publications

(67 citation statements)

References 56 publications

(51 reference statements)

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“…The 193 relevant articles were searched, of which 34 studies were eligible for inclusion, based on title and abstract. After assessment of the full text articles, 20 relevant articles (19 in English [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and 1 in Chinese [42]) including 5911 patients were available. A list of all the details abstracted from included studies was provided in table 1.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

Gao¹,

Li²,

Tian³

et al. 2012

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Serum markers are needed to be developed to specifically diagnose Hepatocellular carcinoma (HCC). Des-γ-carboxy prothrombin (DCP) is a promising tool with limited expense and widely accessibility, but the reported results have been controversial. In order to review the performance of DCP for the diagnosis of HCC, the meta-analysis was performed. After a systematic review of relevant studies, the sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively) were pooled using a bivariate meta-analysis. Potential between-study heterogeneity was explored by meta-regression model. The post-test probability and the likelihood ratio scattergram to evaluate clinical usefulness were calculated. Based on literature review of 20 publications, the overall sensitivity, specificity, PLR and NLR of DCP for the detection of HCC were 67% (95%CI, 58%-74%), 92% (95%CI, 88%-94%), 7.9 (95%CI, 5.6-11.2) and 0.36 (95%CI, 0.29-0.46), respectively. The area under the bivariate summary receiving operating characteristics curve was 0.89 (95%CI, 0.85-0.92). Significant heterogeneity was present. In conclusion, the major role of DCP is the moderate confirmation of HCC. More prospective studies of DCP are needed in future.

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Section: Resultsmentioning

confidence: 99%

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

Gao¹,

Li²,

Tian³

et al. 2012

neo

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“…The development of the AFP-L3 assay has increased the sensitivity and specificity of AFP (39) because it retains significant discriminatory ability even at low levels of total AFP (13,(40)(41)(42)(43). The recent development of highly sensitive AFP-L3 using an automated microfluidic based assay has made the isoform even more sensitive and specific (13,34).…”

Section: Discussionmentioning

confidence: 99%

The Detection of Hepatocellular Carcinoma Using a Prospectively Developed and Validated Model Based on Serological Biomarkers

Johnson¹,

Pirrie

Cox³

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers.Methods: A total of 670 patients with either CLD alone or hepatocellular carcinoma were recruited from a single UK center into a case-control study. Sera were collected prospectively and specifically for this study. A logistic regression analysis was used to determine independent factors associated with hepatocellular carcinoma and a model built and assessed in terms of sensitivity, specificity, and proportion of correct diagnoses.Results: The final model involving gender, age, AFP-L3, a fetoprotein (AFP), and des-carboxy-prothrombin ("GALAD") was developed in a "discovery" data set and validated in independent data sets both from the same institution and from an external institution. When optimized for sensitivity and specificity, the model gave values of more than 0.88 irrespective of the disease stage.Conclusions: The presence of hepatocellular carcinoma can be detected in patients with CLD on the basis of a model involving objective clinical and serological factors. It is now necessary to test the model's performance in a prospective manner and in a routine clinical practice setting, to determine if it may replace or, more likely, enhance current radiological approaches.Impact: Our data provide evidence that an entirely objective serum biomarker-based model may facilitate the detection and diagnosis of hepatocellular carcinoma and form the basis for a prospective study comparing this approach with the standard radiological approaches. Cancer Epidemiol Biomarkers Prev; 23(1); 144-53. Ó2013 AACR.

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“…AFP has been the core biomarker for HCC, but because of the low sensitivity of the biomarker guidelines of the American Association for the Study of Liver Diseases do not include the usage of the AFP test for HCC surveillance for high-risk patients (27). AFP-L 3 %, an LCA-retained fuco-fraction of AFP, has been suggested as a means to complement the unsatisfactory clinical outcomes that are particularly observed for HCC patients with low AFP serum level (28,29). However, studies failed to support the increased validity of AFP-L 3 % over the use of AFP alone.…”

Section: Discussionmentioning

confidence: 99%

Semi-quantitative Measurement of a Specific Glycoform Using a DNA-tagged Antibody and Lectin Affinity Chromatography for Glyco-biomarker Development *

Cho

Kim

Kang

et al. 2015

Molecular & Cellular Proteomics

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Aberrant glycosylation-targeted disease biomarker development is based on cumulative evidence that certain glycoforms are mass-produced in a disease-specific manner. However, the development process has been hampered by the absence of an efficient validation method based on a sensitive and multiplexed platform. In particular, ELISA-based analytical tools are not adequate for this purpose, mainly because of the presence of a pair of N-glycans of IgG-type antibodies. To overcome the associated hurdles in this study, antibodies were tagged with oligonucleotides with T7 promoter and then allowed to form a complex with corresponding antigens. An antibody-bound specific glycoform was isolated by lectin chromatography and quantitatively measured on a DNA microarray chip following production of fluorescent RNA by T7-trascription. This tool ensured measurement of targeted glycoforms of multiple biomarkers with high sensitivity and multiplexity. This analytical method was applied to an in vitro diagnostic multivariate index assay where a panel of hepatocellular carcinoma (HCC) biomarkers comprising alpha-fetoprotein, hemopexin, and alpha-2-macroglobulin (A2M) was examined in terms of the serum level and their fuco-fractions. The results indicated that the tests using the multiplexed fuco-biomarkers provided improved discriminatory power between non-hepatocellular carcinoma and hepatocellular carcinoma subjects compared with the alpha-fetoprotein level or fuco-alphafetoprotein test alone. The developed method is expected

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Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma

Cited by 120 publications

References 56 publications

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

The Detection of Hepatocellular Carcinoma Using a Prospectively Developed and Validated Model Based on Serological Biomarkers

Semi-quantitative Measurement of a Specific Glycoform Using a DNA-tagged Antibody and Lectin Affinity Chromatography for Glyco-biomarker Development *

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Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma

Cited by 120 publications

References 56 publications

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

The Detection of Hepatocellular Carcinoma Using a Prospectively Developed and Validated Model Based on Serological Biomarkers

Semi-quantitative Measurement of a Specific Glycoform Using a DNA-tagged Antibody and Lectin Affinity Chromatography for Glyco-biomarker Development *

Contact Info

Product

Resources

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Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis

Diagnostic performance of Des-γ-carboxy prothrombin (DCP) for Hepatocellular carcinoma: A Bivariate Meta-analysis