Dataset Information

Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis.

ABSTRACT: Elevated serum alpha-fetoprotein (AFP) can be observed in liver cirrhosis and hepatocellular carcinoma (HCC). The glycosylation patterns of AFP have been shown to differentiate these conditions, with AFP glycoforms with core fucosylation (AFP-L3) serving as a malignancy risk predictor for HCC. We have developed a method to detect endogenously present AFP proteoforms and to quantify the relative abundance of AFP-L3 glycoforms (AFP-L3%) in serum samples. This method consists of immune enrichment of endogenous AFP, followed by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) intact protein analysis of AFP. Data are available via ProteomeXchange with identifier PXD038606. Based on the AFP profiles in authentic patient serum samples, we have identified that the frequently observed AFP glycoforms without core fucosylation (AFP-L1) are G2S2 and G2S1, and common AFP-L3 glycoforms are G2FS1 and G2FS2. The intensities of glycoforms in the deconvoluted spectrum are used to quantify AFP-L3% in each sample. The method evaluation included reproducibility, specificity, dilution integrity, and comparison of AFP-L3% with a lectin-binding gel shift electrophoresis (GSE) assay. The AFP-L1 and AFP-L3 proteoforms were reproducibly identified in multiple patient serum samples, resulting in reproducible AFP-L3% quantification. There was considerable agreement between the developed LC-HRMS and commercial GSE methods when quantifying AFP-L3% (Pearson r = 0.63) with a proportional bias.

SUBMITTER: Dunbar C

PROVIDER: S-EPMC9830635 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis.

Dunbar Carmen C Kushnir Mark M MM Yang Yifei K YK

Journal of proteome research 20221221 1

Elevated serum alpha-fetoprotein (AFP) can be observed in liver cirrhosis and hepatocellular carcinoma (HCC). The glycosylation patterns of AFP have been shown to differentiate these conditions, with AFP glycoforms with core fucosylation (AFP-L3) serving as a malignancy risk predictor for HCC. We have developed a method to detect endogenously present AFP proteoforms and to quantify the relative abundance of AFP-L3 glycoforms (AFP-L3%) in serum samples. This method consists of immune enrichment o ...[more]

PMID: 36541409

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Project description:BackgroundScreening of early hepatocellular carcinoma (HCC) diagnosis is the greatest challenge for hepatologists. Alpha?-fetoprotein (AFP) is the most common non-invasive biomarker used in HCC diagnosis.Objectives and AimsTo make a comparison between the new biomarker Golgi protein 73 (GP73) versus the standard biomarker AFP in the diagnosis of HCC.MethodsOur study was a case–control study, and 60 patients were included in the study. They were divided into two groups: ?1) HCC patients with either chronic HBV or HCV infection (n=30); and ?2) ?non-HCC patients with HBV or HCV infection who had either chronic hepatitis or liver cirrhosis (n=30). In addition, 30 healthy volunteers were included as a control group. Patients were subjected to liver function tests, kidney function tests, serum Golgi protein 73 and AFP levels. Imaging diagnosis of HCC was done by ?computed ?tomography (CT) or ?magnetic ?resonance ?imaging (MRI) based on American Association for the Study of Liver Diseases (AASLD) ?practice ?guidelines.ResultsStatistically significant differences between groups in terms of serum AFP (p<0.001) and GP73 (p<0.001) were found. Non-HCC patients (chronic hepatitis and liver cirrhosis) and HCC patients had significantly higher AFP and GP73 than the control group. In addition, patients with HCC had significantly higher AFP and GP73 than chronic hepatitis and cirrhotic patients. GP73 had higher diagnostic performance than AFP. At a cut-off value of ?8.4 ng/mL, GP73 yielded a sensitivity of 86.7% and specificity of 89% for the discrimination between HCC and normal populations. Similarly, at a cut-off value of ?8.45 ng/mL, GP73 yielded a sensitivity of 83.3% and specificity of 84% for the discrimination between HCC patients and non?-HCC patients. On the other hand, AFP at a cut-off value of ?2.4 ng/mL yielded a sensitivity of 75.4% and specificity of 90% for the discrimination between HCC and normal populations?; and at a cut-off value of ?20.85 ng/mL, AFP yielded a sensitivity of 72.2% and specificity of 86.2% for the discrimination between HCC and non-HCC patients.ConclusionGolgi protein 73 is a promising and accurate biomarker for early detection of HCC.

Dataset Information

Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis.

Publications

Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis.

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