N-Linked Glycan Branching and Fucosylation Are Increased Directly in Hcc Tissue As Determined through in Situ Glycan Imaging

West, Connor A.; Wang, Mengjun; Herrera, Harmin; Liang, Hongyan; Black, Alyson; Angel, Peggi; Drake, Richard; Mehta, Anand

doi:10.1021/acs.jproteome.8b00323

Cited by 64 publications

(66 citation statements)

References 58 publications

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“…FlexImaging‐generated glycan images normalized to total ion current were then searched using accurate mass against a database of known glycans generated using GlycoWorkbench. Glycan structures annotated in this paper are compositionally accurate as determined by mass as well as prior structural characterizations by MALDI‐FTICR MS, or MALDI–time‐of‐flight mass spectrometry (MALDI‐TOF MS), and liquid chromatography‐MS/MS . A key to monosaccharide unit symbols used to construct depictions of glycan structures is provided in Figure S1.…”

Section: Methodsmentioning

confidence: 99%

Defining the human kidney N‐glycome in normal and cancer tissues using MALDI imaging mass spectrometry

et al. 2020

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Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence. Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined. Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays. Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features. Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues. These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri-and tetra-antennary structures and varying levels of fucosylation and sialylation. A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions. Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes. The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues. These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers. K E Y W O R D Sclear-cell renal cell carcinoma, fucosylation, MALDI imaging, N-glycosylation, polycystic kidney disease

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Section: Methodsmentioning

confidence: 99%

Defining the human kidney N‐glycome in normal and cancer tissues using MALDI imaging mass spectrometry

et al. 2020

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“…These glycans were found to be with increased levels of fucosylation and/or with increased levels of branching. They also found that increased levels of fucosylated glycoforms were associated with a reduction in survival time (West et al, ).…”

Section: Discovery—mass Spectrometry‐based Assaysmentioning

confidence: 97%

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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“…5,43 An increase in the fucosylation levels coupled with increasing levels of fucosylated glycoforms observed in the h most common cancer-hepatocellular carcinoma can be utilized for early detection of the disease. 44 The signicance of sialylation and sialylated glycans in breast cancer brain metastasis was studied. 45 Changes in glycosylation emerge due to the alteration in expression levels of glycosyltransferases in the Golgi compartment of tumor cells.…”

Section: Viral Pathogensmentioning

confidence: 99%

Decoding glycans: deciphering the sugary secrets to be coherent on the implication

Sharma

Shekhar

et al. 2020

RSC Adv.

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N-Linked Glycan Branching and Fucosylation Are Increased Directly in Hcc Tissue As Determined through in Situ Glycan Imaging

Cited by 64 publications

References 58 publications

Defining the human kidney N‐glycome in normal and cancer tissues using MALDI imaging mass spectrometry

Defining the human kidney N‐glycome in normal and cancer tissues using MALDI imaging mass spectrometry

Glycoproteomic markers of hepatocellular carcinoma‐mass spectrometry based approaches

Decoding glycans: deciphering the sugary secrets to be coherent on the implication

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