Evaluation of the potential of Pap test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics

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Abstract

Background: The purpose of this study was to determine whether the residual fixative from a liquid-based Pap test or a swab of the cervix contained proteins that were also found in the primary tumor of a woman with high grade serous ovarian cancer. This study is the first step in determining the feasibility of using the liquid-based Pap test or a cervical swab for the detection of ovarian cancer protein biomarkers. Methods: Proteins were concentrated by acetone precipitation from the cell-free supernatant of the liquid-based Pap test fixative or eluted from the cervical swab. Protein was also extracted from the patient’s tumor tissue. The protein samples were digested into peptides with trypsin, then the peptides were run on 2D-liquid chromatography mass spectrometry (2D-LCMS). The data was searched against a human protein database for the identification of peptides and proteins in each biospecimen. The proteins that were identified were classified for cellular localization and molecular function by bioinformatics integration. Results: We identified almost 5000 proteins total in the three matched biospecimens. More than 2000 proteins were expressed in each of the three biospecimens, including several known ovarian cancer biomarkers such as CA125, HE4, and mesothelin. By Scaffold analysis of the protein Gene Ontology categories and functional analysis using PANTHER, the proteins were classified by cellular localization and molecular function, demonstrating that the Pap test fluid and cervical swab proteins are similar to each other, and also to the tumor extract. Conclusions: Our results suggest that Pap test fixatives and cervical swabs are a rich source of tumor-specific biomarkers for ovarian cancer, which could be developed as a test for ovarian cancer detection.

Original languageEnglish (US)
Article number4
JournalClinical Proteomics
Volume18
Issue number1
DOIs
StatePublished - Jan 7 2021

Bibliographical note

Funding Information:
We acknowledge the contributions of members of the University of Minnesota Core facilities to this project: the University of Minnesota Center for Mass Spectrometry and Proteomics (Dr. LeeAnn Higgins and Todd Markowski), and the BioNet Tissue Procurement Facility (partially funded by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494). We are also grateful to BD for providing cervical brooms and SurePath? liquid Pap test vials for this research study. This research was performed in the laboratories of the Ovarian Cancer Early Detection Program at the University of Minnesota (z.umn.edu/OCEDP).

Funding Information:
This project was supported by funding from the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award #W81XWH-16-1-0070.

Funding Information:
We acknowledge the contributions of members of the University of Minnesota Core facilities to this project: the University of Minnesota Center for Mass Spectrometry and Proteomics (Dr. LeeAnn Higgins and Todd Markowski), and the BioNet Tissue Procurement Facility (partially funded by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494). We are also grateful to BD for providing cervical brooms and SurePath™ liquid Pap test vials for this research study. This research was performed in the laboratories of the Ovarian Cancer Early Detection Program at the University of Minnesota (z.umn.edu/OCEDP).

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Biomarker
  • Mass spectrometry based proteomics
  • Ovarian cancer detection
  • Pap test

PubMed: MeSH publication types

  • Journal Article

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