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Revealing the human mucinome.

Stacy A Malaker1,2, Nicholas M Riley3, D Judy Shon3

  • 1Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, 94305, CA, USA. stacy.malaker@yale.edu.

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|June 20, 2022
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Summary
This summary is machine-generated.

Researchers developed a mucinomics platform using inactive StcE to identify mucin-domain glycoproteins. This approach reveals key cancer molecular signatures in ovarian cancer patients.

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Area of Science:

  • Biochemistry
  • Glycobiology
  • Proteomics

Background:

  • Mucin domains are crucial O-glycosylated protein structures involved in various human diseases.
  • The full extent of the mucinome (all mucin-domain glycoproteins) is not yet well-defined.
  • Bacterial O-glycoprotease StcE and its inactive mutant show selective binding to mucin-domain glycoproteins.

Purpose of the Study:

  • To develop a mucinomics platform for selective enrichment and identification of mucin-domain glycoproteins.
  • To utilize inactive StcE as a tool for mucinome characterization.
  • To identify molecular signatures of cancer in patient samples.

Main Methods:

  • Leveraging an inactive point mutant of bacterial O-glycoprotease StcE for selective enrichment.
  • Analyzing complex biological samples including cell lysate and ovarian cancer patient ascites fluid.
  • Employing an algorithm to assign confidence to identified mucin-domain glycoprotein hits.

Main Results:

  • Successful enrichment and identification of mucin-domain glycoproteins from complex samples.
  • Detection of hundreds of glycopeptides from mucin domains.
  • Identification of overlapping mucin-domain glycoprotein populations in ovarian cancer patients.
  • Demonstration of the platform's ability to reveal cancer-specific molecular signatures.

Conclusions:

  • The developed mucinomics platform enables comprehensive characterization of the mucinome.
  • Inactive StcE is an effective tool for selective enrichment of mucin-domain glycoproteins.
  • This approach can identify critical molecular signatures of cancer in vitro and ex vivo.