Abstract
BackgroundThe 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.MethodsProteins 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.ResultsWe 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.ConclusionsOur 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.
Highlights
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 found in the primary tumor of a woman with high grade serous ovarian cancer
Comparison of the proteins identified in the three biospecimens We compared the proteins identified by Two dimensional (2D)-LC mass spectrometry (MS)/MS from three biospecimens from a patient with high grade serous ovarian cancer: primary tumor tissue, a cervical swab, and the residual, cell-free fixative from a liquidbased SurePathTM Pap test
We have previously shown that the cell-free supernatant from residual Pap tests contained sufficient protein for analysis by 2D-Liquid chromatography mass spectrometry (LCMS), and identified 153 proteins from patients with normal cervical cytology in a “Normal Pap test Core Proteome” [8]
Summary
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 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. Barriers to the development of a screening tool include: the low prevalence of ovarian cancer in the general population, the inaccessibility of the ovaries to direct evaluation, nonspecificity of known tumor markers (such as CA125) [1], Boylan et al Clin Proteom (2021) 18:4 and the absence of known risk factors (such as high-risk genetic mutations) for the majority of patients. We hypothesized that proteins shed by ovarian cancer cells can be detected during routine Pap tests by mass spectrometry (MS)-based proteomics. The use of biospecimens proximal to the tumor site improves biomarker detection [7]; the proposed strategy takes advantage of the proximity of the cervix to the ovary (i.e. proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening), and uses already-obtained diagnostic material, which may help with cost-containment and accessibility
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
