Targeted selected reaction monitoring verifies histology specific peptide signatures in epithelial ovarian cancer
(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
- Liljedahl, Leena LU ; Malmström, Johan LU ; Kristjansdottir, Björg ; Waldemarson, Sofia LU and Sundfeldt, Karin
- organization
- publishing date
- 2021-11-01
- 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
-
- scopus:85118947507
- pmid:34830868
- 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}}, }