Serum alpha fetoprotein heterogeneity as a means of differentiating between primary hepatocellular carcinoma and hepatic secondaries

Pk, Buamah; Gibb, I; Bates, Gillian; Am, Ward

doi:10.1016/0009-8981(84)90277-8

Cited by 43 publications

(23 citation statements)

References 5 publications

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“…AFP is currently the only clinical marker which has been widely used for serological diagnosis of human HCC (36). However, its specificity is low, especially for chronic liver diseases and cirrhosis, and its sensitivity shows only 60 to 80% at cutoff value of 20 g/L in serum (37). As it is urgent to find another noninvasive, reliable method for detecting HCC as early as possible, the application of high-throughput screening technologies like proteomics is becoming the trend in biomarker discovery.…”

Section: Resultsmentioning

confidence: 99%

Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma

Chen

Tan

Wang

et al. 2011

Molecular & Cellular Proteomics

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A robust, reproducible, and high throughput method was developed for the relative quantitative analysis of glycoprotein abundances in human serum. Instead of quantifying glycoproteins by glycopeptides in conventional quantitative glycoproteomics, glycoproteins were quantified by nonglycosylated peptides derived from the glycoprotein digest, which consists of the capture of glycoproteins in serum samples and the release of nonglycopeptides by trypsin digestion of captured glycoproteins followed by two-dimensional liquid chromatography-tandem MS analysis of released peptides. Protein quantification was achieved by comparing the spectrum counts of identified nonglycosylated peptides of glycoproteins between different samples. This method was demonstrated to have almost the same specificity and sensitivity in glycoproteins quantification as capture at glycopeptides level. The differential abundance of proteins present at as low as nanogram per milliliter levels was quantified with high confidence. The established method was applied to the analysis of human serum samples from healthy people and patients with hepatocellular carcinoma (HCC) to screen differential glycoproteins in HCC. Thirty eight glycoproteins were found with substantial concentration changes between normal and HCC serum samples, including ␣-fetoprotein, the only clinically used marker for HCC diagnosis. The abundance changes of three glycoproteins, i.e. galectin-3 binding protein, insulin-like growth factor binding protein 3, and thrombospondin 1, which were associated with the development of HCC, were further confirmed by enzyme-linked immunosorbent assay. In conclusion, the developed method was an effective approach to quantitatively analyze glycoproteins in human serum and could be further applied in the biomarker discovery for HCC and other cancers. Molecular

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Section: Resultsmentioning

confidence: 99%

Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma

Chen

Tan

Wang

et al. 2011

Molecular & Cellular Proteomics

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“…The numbers of cases studied are shown in parentheses. tography of AFP extracted from renal tumor tissue [17], Increased AFP-C1 is commonly observed in extrahepatic tumors [15,20], However, the present case of renal cell carci noma was devoid of AFP-L2, which is another characteristic band of extrahepatic tumors, and also lacked AFP-L3, a fucosylated AFP, which increases commonly in neoplastic conditions [15]. Those lectinreactive patterns of AFP were entirely differ ent from those of AFP produced by fetal kid ney cells [16].…”

Section: Discussionmentioning

confidence: 99%

Lectin Reactivity of Alpha-Fetoprotein in a Case of Renal Cell Carcinoma

Taketa¹,

Ichikawa²,

Sakuda³

et al. 1989

Tumor Biol

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The increased serum level of α-fetoprotein (AFP) in a case of renal cell carcinoma, a rare condition of AFP production by mesoderm-derived cells, was evaluated for its lectin reactivity by affinity electrophoresis, followed by the antibody-affinity transfer to nitrocellulose membranes for visualization of separated AFP bands. The AFP of this case was characterized by relative increases of concanavalin A-nonreactive AFP-C1 (60.4%), erythroagglutinating phytohemagglutinin-reactive AFP-P4 (37.8%) and AFP-P5 (46.3%) and Allomyrina dichotoma lectin-nonreactive AFP-A1s (66.7%), and by the total absence of lentil lectin-reactive components, AFP-L2 and AFP-L3. Thus, the lectin-reactive pattern of AFP markedly deviated not only from that of cord serum, but also from those of other malignancies and of fetal kidney cells in culture.

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“…Because there is a correlation between elevated levels of ␣-fetoprotein (AFP) and the occurrence of HCC, determination of AFP levels is often included as a serum marker of disease (4). However, AFP as a sole indicator of HCC is of limited value, often being elevated in the absence of serious disease and not elevated in as many as 50% of liver cancers (5).…”

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confidence: 99%

Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans

Block

Comunale²,

Lowman³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

348

323

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Chronic infection with hepatitis B virus (HBV) is associated with the majority of hepatocellular carcinoma (HCC).The diagnosis of HCC is usually made in the late stages of the disease, when treatment options are limited and prognosis is poor. We therefore have developed a method of glycoproteomic analysis in an attempt to discover serum markers that can assist in the early detection of HBV-induced liver cancer. Briefly, a comparative method for analysis of oligosaccharides released from serum glycoproteins and for recovery and identification of proteins with aberrant glycosylation, as a function of cancer diagnosis, is described. The model we have used is the woodchuck (Marmota monax), which shares similarities in the glycosylation pattern associated with liver proteins in human HCC. In this report, we show that woodchucks diagnosed with HCC have dramatically higher levels of serumassociated core ␣-1,6-linked fucose, as compared with woodchucks without a diagnosis of HCC. The coupling of this methodology with 2D gel proteomics has permitted the identification of several glycoproteins with altered glycosylation as a function of cancer. One such glycoprotein, Golgi Protein 73 (GP73), was found to be elevated and hyperfucosylated in animals with HCC. Further, the study showed GP73 to be elevated in the serum of people with a diagnosis of HCC, providing a validation of our approach. The potential of this technology for biomarker discovery and the implications of increased levels of GP73 in liver cancer are discussed.glycomics ͉ hepatitis B virus ͉ hepatocellular carcinoma ͉ proteomics

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Serum alpha fetoprotein heterogeneity as a means of differentiating between primary hepatocellular carcinoma and hepatic secondaries

Cited by 43 publications

References 5 publications

Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma

Development of Glycoprotein Capture-Based Label-Free Method for the High-throughput Screening of Differential Glycoproteins in Hepatocellular Carcinoma

Lectin Reactivity of Alpha-Fetoprotein in a Case of Renal Cell Carcinoma

Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans

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