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Targeted selected reaction monitoring verifies histology specific peptide signatures in epithelial ovarian cancer

Liljedahl, Leena LU ; Malmström, Johan LU orcid ; Kristjansdottir, Björg ; Waldemarson, Sofia LU and Sundfeldt, Karin (2021) In Cancers 13(22).
Abstract

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 (n = 74). Unsupervised and supervised multivariate analyses were used for comparisons. The... (More)

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 (n = 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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Early-stage diagnostics, Epithelial ovarian cancer (OC), Proteomics, Targeted selected reaction monitoring (SRM)
in
Cancers
volume
13
issue
22
article number
5713
publisher
MDPI AG
external identifiers
  • pmid:34830868
  • scopus:85118947507
ISSN
2072-6694
DOI
10.3390/cancers13225713
language
English
LU publication?
yes
id
3d5dc09b-7940-45b3-9b85-d63fe745e910
date added to LUP
2021-11-20 12:56:55
date last changed
2024-06-15 20:54:29
@article{3d5dc09b-7940-45b3-9b85-d63fe745e910,
  abstract     = {{<p>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 (n = 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.</p>}},
  author       = {{Liljedahl, Leena and Malmström, Johan and Kristjansdottir, Björg and Waldemarson, Sofia and Sundfeldt, Karin}},
  issn         = {{2072-6694}},
  keywords     = {{Biomarkers; Early-stage diagnostics; Epithelial ovarian cancer (OC); Proteomics; Targeted selected reaction monitoring (SRM)}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{22}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Targeted selected reaction monitoring verifies histology specific peptide signatures in epithelial ovarian cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers13225713}},
  doi          = {{10.3390/cancers13225713}},
  volume       = {{13}},
  year         = {{2021}},
}