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An Integrated Approach to Protein Discovery and Detection From Complex Biofluids

Ovarian cancer, a leading cause of cancer-related deaths among women, has been notoriously difficult to screen for and diagnose early, as early detection significantly improves survival. Researchers and clinicians seek routinely usable and noninvasive screening methods; however, available methods (i...

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Autores principales: Luu, Gordon T., Ge, Chang, Tang, Yisha, Li, Kailiang, Cologna, Stephanie M., Godwin, Andrew K., Burdette, Joanna E., Su, Judith, Sanchez, Laura M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388710/
https://www.ncbi.nlm.nih.gov/pubmed/37301378
http://dx.doi.org/10.1016/j.mcpro.2023.100590
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author Luu, Gordon T.
Ge, Chang
Tang, Yisha
Li, Kailiang
Cologna, Stephanie M.
Godwin, Andrew K.
Burdette, Joanna E.
Su, Judith
Sanchez, Laura M.
author_facet Luu, Gordon T.
Ge, Chang
Tang, Yisha
Li, Kailiang
Cologna, Stephanie M.
Godwin, Andrew K.
Burdette, Joanna E.
Su, Judith
Sanchez, Laura M.
author_sort Luu, Gordon T.
collection PubMed
description Ovarian cancer, a leading cause of cancer-related deaths among women, has been notoriously difficult to screen for and diagnose early, as early detection significantly improves survival. Researchers and clinicians seek routinely usable and noninvasive screening methods; however, available methods (i.e., biomarker screening) lack desirable sensitivity/specificity. The most fatal form, high-grade serous ovarian cancer, often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified cystatin A, which was validated in an animal model. To overcome the limits of detection inherent to mass spectrometry, we demonstrated that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator and translated our workflow to patient-derived clinical samples, highlighting the potential utility of early stage detection where biomarker levels would be low.
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spelling pubmed-103887102023-08-01 An Integrated Approach to Protein Discovery and Detection From Complex Biofluids Luu, Gordon T. Ge, Chang Tang, Yisha Li, Kailiang Cologna, Stephanie M. Godwin, Andrew K. Burdette, Joanna E. Su, Judith Sanchez, Laura M. Mol Cell Proteomics Research Ovarian cancer, a leading cause of cancer-related deaths among women, has been notoriously difficult to screen for and diagnose early, as early detection significantly improves survival. Researchers and clinicians seek routinely usable and noninvasive screening methods; however, available methods (i.e., biomarker screening) lack desirable sensitivity/specificity. The most fatal form, high-grade serous ovarian cancer, often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified cystatin A, which was validated in an animal model. To overcome the limits of detection inherent to mass spectrometry, we demonstrated that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator and translated our workflow to patient-derived clinical samples, highlighting the potential utility of early stage detection where biomarker levels would be low. American Society for Biochemistry and Molecular Biology 2023-06-09 /pmc/articles/PMC10388710/ /pubmed/37301378 http://dx.doi.org/10.1016/j.mcpro.2023.100590 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research
Luu, Gordon T.
Ge, Chang
Tang, Yisha
Li, Kailiang
Cologna, Stephanie M.
Godwin, Andrew K.
Burdette, Joanna E.
Su, Judith
Sanchez, Laura M.
An Integrated Approach to Protein Discovery and Detection From Complex Biofluids
title An Integrated Approach to Protein Discovery and Detection From Complex Biofluids
title_full An Integrated Approach to Protein Discovery and Detection From Complex Biofluids
title_fullStr An Integrated Approach to Protein Discovery and Detection From Complex Biofluids
title_full_unstemmed An Integrated Approach to Protein Discovery and Detection From Complex Biofluids
title_short An Integrated Approach to Protein Discovery and Detection From Complex Biofluids
title_sort integrated approach to protein discovery and detection from complex biofluids
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388710/
https://www.ncbi.nlm.nih.gov/pubmed/37301378
http://dx.doi.org/10.1016/j.mcpro.2023.100590
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