Direct Monitoring of Fucosylated Glycopeptides of Alpha‐Fetoprotein in Human Serum for Early Hepatocellular Carcinoma by Liquid Chromatography–Tandem Mass Spectrometry with Immunoprecipitation

Kim, Kwang Hoe; Lee, Soo-Youn; Hwang, Heeyoun; Lee, Ju‐Yeon; Ji, Eun Sun; An, Hyun Joo; Kim, Jin Young; Yoo, Jong Shin

doi:10.1002/prca.201800062

Cited by 23 publications

(41 citation statements)

References 35 publications

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“…Most recently, An and coworkers (Kim et al, ) developed a quantitative LC‐MS/MS‐PRM to monitor fucosylated glycopeptides in serum AFP to distinguish between HCC and cirrhosis patients. Because AFP is normally present at low levels in serum, even in patients with liver disease, a more sensitive approach is required.…”

Section: Verification Lc‐mrm Analysis Of Glycosylationmentioning

confidence: 99%

“…With a combination of these approaches, the MS detection limit was significantly improved (LOD < 2 ng/mL). The result showed that the relative percentage of fucosylated AFP (AFP‐fuc%) had a better performance than serum AFP levels to differentiate early‐HCC and cirrhosis (AUC = 0.962) with a sensitivity of 92.3% (Kim et al, ).…”

Section: Verification Lc‐mrm Analysis Of Glycosylationmentioning

confidence: 99%

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Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Zhu¹,

Warner²,

Parikh³

et al. 2018

Mass Spectrometry Reviews

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Hepatocellular carcinoma (HCC) is the third most‐common cause of cancer‐related death worldwide. Most cases of HCC develop in patients that already have liver cirrhosis and have been recommended for surveillance for an early onset of HCC. Cirrhosis is the final common pathway for several etiologies of liver disease, including hepatitis B and C, alcohol, and increasingly non‐alcoholic fatty liver disease. Only 20–30% of patients with HCC are eligible for curative therapy due primarily to inadequate early‐detection strategies. Reliable, accurate biomarkers for HCC early detection provide the highest likelihood of curative therapy and survival; however, current early‐detection methods that use abdominal ultrasound and serum alpha fetoprotein are inadequate due to poor adherence and limited sensitivity and specificity. There is an urgent need for convenient and highly accurate validated biomarkers for HCC early detection. The theme of this review is the development of new methods to discover glycoprotein‐based markers for detection of HCC with mass spectrometry approaches. We outline the non‐mass spectrometry based methods that have been used to discover HCC markers including immunoassays, capillary electrophoresis, 2‐D gel electrophoresis, and lectin‐FLISA assays. We describe the development and results of mass spectrometry‐based assays for glycan screening based on either MALDI‐MS or ESI analysis. These analyses might be based on the glycan content of serum or on glycan screening for target molecules from serum. We describe some of the specific markers that have been developed as a result, including for proteins such as Haptoglobin, Hemopexin, Kininogen, and others. We discuss the potential role for other technologies, including PGC chromatography and ion mobility, to separate isoforms of glycan markers. Analyses of glycopeptides based on new technologies and innovative softwares are described and also their potential role in discovery of markers of HCC. These technologies include new fragmentation methods such as EThcD and stepped HCD, which can identify large numbers of glycopeptide structures from serum. The key role of lectin extraction in various assays for intact glycopeptides or their truncated versions is also described, where various core‐fucosylated and hyperfucosylated glycopeptides have been identified as potential markers of HCC. Finally, we describe the role of LC‐MRMs or lectin‐FLISA MRMs as a means to validate these glycoprotein markers from patient samples. These technological advancements in mass spectrometry have the potential to lead to novel biomarkers to improve the early detection of HCC.

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Section: Verification Lc‐mrm Analysis Of Glycosylationmentioning

confidence: 99%

Section: Verification Lc‐mrm Analysis Of Glycosylationmentioning

confidence: 99%

Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Zhu¹,

Warner²,

Parikh³

et al. 2018

Mass Spectrometry Reviews

View full text Add to dashboard Cite

show abstract

“…First, we selected target glycopeptides that are predominant in HCC patients, for determining the relative percent of fucosylation as in our previous report [13]. The target glycopeptides for LC‐PRM MS analysis are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…All samples were prepared as described in our previous report [13]. Briefly, 63 μL (6.3 mg) of resuspended tosyl‐activated Dynabeads MyOne magnetic beads was washed by a coating buffer (0.1 M sodium borate, pH 9.5).…”

Section: Methodsmentioning

confidence: 99%

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Measuring fucosylated alpha‐fetoprotein in hepatocellular carcinoma: A comparison of μTAS and parallel reaction monitoring

Kim

Lee

Baek³

et al. 2021

Proteomics Clinical Apps

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Purpose: Fucosylation of alpha-fetoprotein (AFP) is closely correlated with the diagnosis of patients with hepatocellular carcinoma (HCC). In current, a micro-total analysis system (μTAS) using immunoassay has been developed for determining fucosylated AFP Experimental Design: We compared two analytical methods, μTAS and liquid chromatography-parallel reaction monitoring mass spectrometry (LC-PRM MS), for the measurement of fucosylated AFP in serum to evaluate the usefulness of the results.For this purpose, serum samples were used (cirrhosis, n = 105; HCC, n = 105), and we have discussed the analytical performance of these two methods Results:We observed a correlation (R 2 = 0.84) between LC-PRM MS and μTAS using samples where fucosylated levels were measured by both methods. The fucosylated level of AFP by LC-PRM MS better differentiated between cirrhosis and HCC patients than those by μTAS (AUC = 0.910 vs. 0.861), particularly in subgroups with a level of total AFP < 20 ng/mL (0.973 vs. 0.874) and in early stage (I and II) patients (0.922 vs. 0.835) Conclusions and Clinical Relevance:From this comparative study we can suggest that the LC-PRM MS is applicable in the measurement of fucosylated AFP from human serum and is more useful for early diagnosis of HCC.Clinical Relevance: Fucosylation of AFP is used for the detection of HCC. A micro-total analysis system (μTAS) has been only developed for measuring fucosylation of AFP in clinical research. This study reports the fucosylation of AFP in human serum samples from cirrhosis and HCC patients using the μTAS and a LC-PRM MS to evaluate fucosylation of AFP from each method. As a result, LC-PRM MS is complementary to the conventional μTAS method. Furthermore, LC-PRM MS provides a higher diagnostic accuracy than the μTAS in patients with low AFP levels and an early stage.

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Abdominal ultrasound and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease

Colli

Nadarević

Miletić

et al. 2021

Cochrane Database of Systematic Reviews

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Direct Monitoring of Fucosylated Glycopeptides of Alpha‐Fetoprotein in Human Serum for Early Hepatocellular Carcinoma by Liquid Chromatography–Tandem Mass Spectrometry with Immunoprecipitation

Abstract: These findings suggest that glycopeptide-based LC-MS/MS is a promising method and that AFP-fuc% is a clinically useful parameter for differentiating between early HCC and liver cirrhosis.

Cited by 23 publications

References 35 publications

Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Measuring fucosylated alpha‐fetoprotein in hepatocellular carcinoma: A comparison of μTAS and parallel reaction monitoring

Abdominal ultrasound and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease

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