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Determination of glycosylation signature

A glycan, substrate technology, applied in the field of glycosylation signature determination, which can solve the problem of underestimating protein levels and false results

Pending Publication Date: 2018-10-23
RANDOX LAB LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This can lead to underestimation of protein levels in samples and false results in diagnostic tests

Method used

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  • Determination of glycosylation signature
  • Determination of glycosylation signature

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Enhanced biomarker detection using lectin / antibody epitopes masked by glycosylation

[0088] Fetuin A detection using lectins and antibodies

[0089] Fetuin A is an acute-phase anti-inflammatory glycoprotein secreted by the liver into the circulation and has been identified as a mediator of growth signaling in breast cancer cells. There are six reported glycosylation sites on fetuin A with four O-linked n-acetylgalactosamine sites for the C-terminus of the protein. The potential of these glycosylation modifications to mask the detection of fetuin A captured in sera from normal or breast cancer patients was assessed. Figure 10 showed that in patients with breast cancer, the n-acetylgalactosamine-containing fetuin A protein was detectable and indeed elevated relative to normal controls using the VVA lectin. However, using a specific detection antibody (called Ab1, Figure 10 B) Instead of detecting similar levels of protein across sample sets, alternative assays (Ab...

Embodiment 2

[0091] Rationale for additional benefit from multiplex analysis of glycoprotein markers

[0092] Detection of pancreatic cancer by a single circulating disease biomarker has been shown to be insufficient due to poor identification of patients with early-stage disease. Thus, the concept has emerged that multifaceted pathology can be reflected in the simultaneous detection of multiple disease markers. Figure 11 A proof of principle for improved diagnostic capability in pancreatic cancer (pancreatic cancer serum samples vs. ROC AUC values ​​for CA19-9, CEA or A1AG.

Embodiment 3

[0094] Examples of Additional Clinical Benefits of Glycosylation

[0095] Improved detection of pancreatic cancer biomarkers in patient serum samples using glycosylation

[0096] A comparison was made between classical immunoturbidimetric total protein and biochip-based detection of glycosylated alpha-1 acid glycoprotein (A1AG). Subsequent analyzes were used to determine the diagnostic ability of each assay platform to identify pancreatic cancer in the developing patient sample cohort. The total protein detection method returned a ROC AUC value of 0.648, which did not reach statistical significance (p: 0.2155, Figure 12 A). In addition, there was no statistically significant difference in total protein overall between pancreatic cancer and normal controls (p: 0.1614, Figure 12 B). However, using the AAL-mediated fucosylated A1AG assay, a significant improvement in ROC output (0.919) was observed, which reached statistical significance (p Figure 12 C). RLU output repre...

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PUM

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Abstract

The present invention describes methods of determining the glycosylation signature and determining the level of a protein in a sample obtained from a patient. The present invention also describes useof a patient protein glycosylation profile to identify the presence or absence of a disease in subjects.

Description

technical field [0001] The present invention relates to methods for determining the profile of glycosylation in a sample and for determining protein levels. The present invention also relates to the use of a patient's protein glycosylation profile for identifying the presence or absence of a disease in a subject. Background technique [0002] Many proteins are glycosylated after translation. This post-translational modification involves the chemical attachment of sugars to proteins through glycosidic bonds to produce glycoproteins. Protein glycosylation can take many forms and is defined according to the type of glycosidic linkages present. [0003] N-linked glycosylation involves attachment of a sugar molecule to a nitrogen (N4) atom in the side chain of an asparagine residue within the consensus sequence Asn-Xaa-Ser / Thr (where Xaa is not proline). This modification occurs in secreted and membrane proteins of eukaryotes and archea, but not in bacteria. The process begin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574
CPCG01N33/57438G01N2333/4724G01N2440/38G01N33/57484
Inventor I·麦康奈尔P·菲茨杰拉德J·拉蒙特C·理查德森
Owner RANDOX LAB LTD
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