Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer

Epithelial ovarian cancer (OC) is a disease with high mortality due to vague early clinical symptoms. Benign ovarian cysts are common and accurate diagnosis remains a challenge because of the molecular heterogeneity of OC. We set out to investigate whether the disease diversity seen in ovarian cyst...

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Autores principales:	Leena Liljedahl, Johan Malmström, Björg Kristjansdottir, Sofia Waldemarson, Karin Sundfeldt
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epithelial ovarian cancer (OC) targeted selected reaction monitoring (SRM) proteomics biomarkers early-stage diagnostics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6709d14dd8e847cc97e3863bd9cd09a2
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spelling	oai:doaj.org-article:6709d14dd8e847cc97e3863bd9cd09a22021-11-25T17:03:02ZTargeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer10.3390/cancers132257132072-6694https://doaj.org/article/6709d14dd8e847cc97e3863bd9cd09a22021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5713https://doaj.org/toc/2072-6694Epithelial ovarian cancer (OC) is a disease with high mortality due to vague early clinical symptoms. Benign ovarian cysts are common and accurate diagnosis remains a challenge because of the molecular heterogeneity of OC. We set out to investigate whether the disease diversity seen in ovarian cyst fluids and tumor tissue could be detected in plasma. Using existing mass spectrometry (MS)-based proteomics data, we constructed a selected reaction monitoring (SRM) assay targeting peptides from 177 cancer-related and classical proteins associated with OC. Plasma from benign, borderline, and malignant ovarian tumors were used to verify expression (<i>n</i> = 74). Unsupervised and supervised multivariate analyses were used for comparisons. The peptide signatures revealed by the supervised multivariate analysis contained 55 to 77 peptides each. The predictive (Q2) values were higher for benign vs. low-grade serous Q2 = 0.615, mucinous Q2 = 0.611, endometrioid Q2 = 0.428 and high-grade serous Q2 = 0.375 (stage I–II Q2 = 0.515; stage III Q2 = 0.43) OC compared to benign vs. all malignant Q2 = 0.226. With targeted SRM MS we constructed a multiplexed assay for simultaneous detection and relative quantification of 185 peptides from 177 proteins in only 20 µL of plasma. With the approach of histology-specific peptide patterns, derived from pre-selected proteins, we may be able to detect not only high-grade serous OC but also the less common OC subtypes.Leena LiljedahlJohan MalmströmBjörg KristjansdottirSofia WaldemarsonKarin SundfeldtMDPI AGarticleepithelial ovarian cancer (OC)targeted selected reaction monitoring (SRM)proteomicsbiomarkersearly-stage diagnosticsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5713, p 5713 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epithelial ovarian cancer (OC) targeted selected reaction monitoring (SRM) proteomics biomarkers early-stage diagnostics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	epithelial ovarian cancer (OC) targeted selected reaction monitoring (SRM) proteomics biomarkers early-stage diagnostics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Leena Liljedahl Johan Malmström Björg Kristjansdottir Sofia Waldemarson Karin Sundfeldt Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
description	Epithelial ovarian cancer (OC) is a disease with high mortality due to vague early clinical symptoms. Benign ovarian cysts are common and accurate diagnosis remains a challenge because of the molecular heterogeneity of OC. We set out to investigate whether the disease diversity seen in ovarian cyst fluids and tumor tissue could be detected in plasma. Using existing mass spectrometry (MS)-based proteomics data, we constructed a selected reaction monitoring (SRM) assay targeting peptides from 177 cancer-related and classical proteins associated with OC. Plasma from benign, borderline, and malignant ovarian tumors were used to verify expression (<i>n</i> = 74). Unsupervised and supervised multivariate analyses were used for comparisons. The peptide signatures revealed by the supervised multivariate analysis contained 55 to 77 peptides each. The predictive (Q2) values were higher for benign vs. low-grade serous Q2 = 0.615, mucinous Q2 = 0.611, endometrioid Q2 = 0.428 and high-grade serous Q2 = 0.375 (stage I–II Q2 = 0.515; stage III Q2 = 0.43) OC compared to benign vs. all malignant Q2 = 0.226. With targeted SRM MS we constructed a multiplexed assay for simultaneous detection and relative quantification of 185 peptides from 177 proteins in only 20 µL of plasma. With the approach of histology-specific peptide patterns, derived from pre-selected proteins, we may be able to detect not only high-grade serous OC but also the less common OC subtypes.
format	article
author	Leena Liljedahl Johan Malmström Björg Kristjansdottir Sofia Waldemarson Karin Sundfeldt
author_facet	Leena Liljedahl Johan Malmström Björg Kristjansdottir Sofia Waldemarson Karin Sundfeldt
author_sort	Leena Liljedahl
title	Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
title_short	Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
title_full	Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
title_fullStr	Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
title_full_unstemmed	Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
title_sort	targeted selected reaction monitoring verifies histology specific peptide signatures in epithelial ovarian cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6709d14dd8e847cc97e3863bd9cd09a2
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Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer

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