Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design—Workflow
2.2. Study Population
2.3. Plasma Sample Preparation
2.4. Selection of Target Peptides and Transitions
2.5. Protein Selection
2.6. Selected Reaction Monitoring Mass Spectrometry
2.7. Multivariate Analyses
2.8. Evaluation of Predictive Value vs. p-Value
3. Results
3.1. Main Results
3.1.1. Histology Specific Peptide Patterns
3.1.2. Multivariate Analysis of the Ovarian Cancer Subgroups
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Histology | n | Grade 1 | Stage 1 | Mean Age (Years) | SD Age (Years) |
---|---|---|---|---|---|
Serous benign | 16 | N/A | N/A | 69 | 8.7 |
Serous borderline | 13 | N/A | I | 51.7 | 18.4 |
LGSC | 4 | low | I–II | 52.3 | 5.7 |
Mucinous | 9 | low | I–II | 67.3 | 7.3 |
Endometrioid 2 | 3 | low | I–II | 76.3 | 9.1 |
Endometrioid 2 | 4 | high | I–II | 59 | 16.2 |
HGSC | 8 | high | I–II | 59.3 | 5.1 |
HGSC | 17 | high | III | 61.5 | 12.1 |
Benign vs. Subgroup | n | OPLS-DA Model-Name (also Figure 2a) | Q2, VIP > 1.0 | #Peptides VIP > 1.0 Unique 1 Peptides | #Peptides p < 0.05 (% Shared with VIP > 1)Unique 2 Peptides |
---|---|---|---|---|---|
All malignant incl. Borderline | 74 | A1 | 0.138 | 63 | 30, q = 0.26 |
All malignant excl. Borderline | 61 | A2 | 0.226 | 61 | 41, q = 0.184 |
Low-grade 1 incl. Borderline | 45 | B1 | 0.221 | 63 | 22, q = 0.298 |
Low-grade 1 excl. Borderline | 33 | B2 | 0.624 | 59 | 37, q = 0.219 |
Borderline type tumor | 29 | B2.4 | 0.247 | 65, 1 0 | 11 (45%) 2 6 q = 0.688 |
Stage I–II (all histologies) | 44 | E1 (B2 + C1.1 + C2.2) | 0.369 | 66 | 39, q = 0.194 |
Endometrioid stage I–II | 20 | B2.1/C1.1 | 0.428 | 61, 1 5 | 17 (100%) 2 5 q = 0.447 |
Mucinous stage I–II | 25 | B2.2 | 0.611 | 77, 1 8 | 41 (95%) 2 9 q = 0.190 |
LGSC stage I–II | 20 | B2.3 | 0.615 | 63, 1 15 | 11 (100%) 2 5 q = 0.567 |
High-grade 1 | 45 | C1 | 0.333 | 55 | 33, q = 0.234 |
HGSC stage I–III | 41 | C2 | 0.375 | 59 | 42, q = 0.193 |
HGSC stage I–II | 24 | C2.2 | 0.513 | 62, 1 9 | 34 (94%) 2 9 q = 0.206 |
HGSC stage III | 33 | C2.3 | 0.43 | 65, 1 8 | 39 (95%) 2 12 q = 0.212 |
Subgroups in Comparison | n | OPLS-DA Model | Q2, VIP > 1.0 | #Peptides VIP > 1.0 | #Peptides p < 0.05 |
---|---|---|---|---|---|
LGSC stage I–II vs. Mucinous stage I–II | 13 | D1 | 0.468 | 71 | 25, q = 0.313 |
Endometrioid stage I–II vs. Mucinous stage I–II | 16 | D2 | 0.356 | 69 | 14, q = 0.465 |
Endometrioid stage I–II vs. LGSC stage I–II | 11 | D3 | 0.654 | 66 | 7, q = 0.761 |
LGSC stage I–II vs. HGSC stage I–II | 12 | D4 | 0.41 | 72 | 9, q = 0.569 |
Endometrioid 1 stage I–II vs. HGSC stage I–II | 15 | D5 | 0.354 | 70 | 9, q = 0.579 |
Mucinous stage I–II vs. HGSC stage I–II | 17 | D6 | 0.356 | 63 | 17, q = 0.436 |
LGSC stage I–II vs. HGSC stage III | 21 | D7 | 0.634 | 65 | 25, q = 0.302 |
Endometrioid 1 stage I–II vs. HGSC stage III | 24 | D8 | 0.388 | 61 | 25, q = 0.33 |
Mucinous stage I–II vs. HGSC stage III | 26 | D9 | 0.379 | 60 | 10, q = 0.658 |
HGSC stage I–II vs. HGSC stage III | 25 | D10 | 0.592 | 66 | 18, q = 0.404 |
Low-grade incl. Borderline vs. High-grade | 58 | E4 | 0.175 | 57 | 24, q = 0.329 |
Low-grade vs. High-grade | 45 | E5 | 0.356 | 63 | 16, q = 0.489 |
LGSC and HGSC stage I–II vs. HGSC stage III | 29 | E6 | 0.612 | 69 | 34, q = 0.241 |
All stage I–II incl. borderline vs. stage III | 58 | E7 | 0.374 | 60 | 47, q = 0.168 |
All stage I–II vs. stage III | 45 | E8 | 0.299 | 57 | 29, q = 0.272 |
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Liljedahl, L.; Malmström, J.; Kristjansdottir, B.; Waldemarson, S.; Sundfeldt, K. Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer. Cancers 2021, 13, 5713. https://doi.org/10.3390/cancers13225713
Liljedahl L, Malmström J, Kristjansdottir B, Waldemarson S, Sundfeldt K. Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer. Cancers. 2021; 13(22):5713. https://doi.org/10.3390/cancers13225713
Chicago/Turabian StyleLiljedahl, Leena, Johan Malmström, Björg Kristjansdottir, Sofia Waldemarson, and Karin Sundfeldt. 2021. "Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer" Cancers 13, no. 22: 5713. https://doi.org/10.3390/cancers13225713