Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer
Abstract
:1. Introduction
2. Results
2.1. Characterization of Extracellular Vesicles in Plasma of EOC Patients and Healthy Controls
2.2. Elevated Levels of Extracellular Vesicles in Serous EOC Patients
2.3. Increased Levels of HLA-GEV in Serous EOC Patients
2.4. Elevated Levels of HLA-GEV Associate with a Detrimental Clinical Profile of Serous EOC Patients
2.5. HLA-GEV Status as a Prognostic Marker for the Prediction of Disease Progression in EOC Patients
3. Discussion
4. Materials and Methods
4.1. Patient Characteristics
4.2. Sampling of Blood
4.3. Selection, Detection and Evaluation of CTCs
4.4. Isolation of Extracellular Vesicles
4.5. EV Characterization by Western Blot
4.6. Nanoparticle Tracking Analysis
4.7. Quantification of Soluble HLA-G Components
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Total | Total EV Amount * n = 70 (%) | HLA-GEV | ||
---|---|---|---|---|
n = 78 (%) | Median [Range] ng/mL | |||
Age | Median: 67 (42–98) | Median: 67 (42–98) | ||
FIGO stage | I–II | 7 (10%) | 7 (9%) | 13.3 [2.9–20.5] |
III | 44 (63%) | 49 (63%) | 13.1 [3.4–60.4] | |
IV | 19 (27%) | 22 (28%) | 19.5 [4.5–44.9] | |
Nodal status | N0 | 16 (23%) | 18 (23%) | 12.9 [2.9–36.7] |
N1 | 32 (46%) | 34 (44%) | 13.6 [3.4–44.9] | |
unknown | 22 (31%) | 26 (33%) | ||
Metastases formation | M0 | 51 (73%) | 56 (72%) | 13.1 [2.9–60.4] |
M1 | 19 (27%) | 22 (28%) | 19.5 [4.5–44.9] | |
Tumor grading | I-II | 27 (39%) | 30 (38%) | 16.3 [4.5–50.7] |
III | 43 (61%) | 48 (62%) | 13.2 [2.9–60.4] | |
Residual tumor | no | 34 (49%) | 37 (47%) | 12.7 [2.9–43.7] |
yes | 36 (51%) | 41 (53%) | 18.7 [4.5–60.4] | |
CTC before therapy | negative | 54 (77%) | 61 (78%) | 13.1 [2.9–60.4] |
positive | 15 (22%) | 16 (21%) | 29.1 [10.4–44.9] | |
unknown | 1 (1%) | 1 (1%) | ||
CTC before therapy | MUC negative | 61 (88%) | 70 (90%) | 13.6 [2.9–60.4] |
MUC positive | 8 (11%) | 7 (9%) | 39.6 [12.2–44.9] | |
unknown | 1 (1%) | 1 (1%) | ||
CTC before therapy | EpCAM negative | 64 (92%) | 73 (94%) | 13.3 [2.9–60.4] |
EpCAM positive | 5 (7%) | 4 (5%) | 32.7 [15.8–44.9] | |
unknown | 1 (1%) | 1 (1%) | ||
CTC after therapy | negative | 17 (24%) | 20 (26%) | 12.8 [5.3–47.8] |
positive | 7 (10%) | 7 (9%) | 12.7 [8.0–44.9] | |
unknown | 46 (66%) | 51 (65%) | ||
DTCs before therapy | negative | 40 (57%) | 46 (59%) | 13.6 [2.9–50.7] |
positive | 28 (40%) | 30 (38%) | 15.0 [6.0–60.4] | |
unknown | 2 (3%) | 2 (3%) | ||
Platinum-based chemotherapy | no resistance | 48 (69%) | 51 (66%) | 13.3 [2.9–60.4] |
resistance | 9 (13%) | 12 (15%) | 15.5 [5.3–44.9] | |
unknown | 13 (18%) | 15 (19%) | ||
Recurrence (10y) | no relapse | 23 (33%) | 24 (31%) | 13.2 [3.4–50.7] |
relapse | 46 (66%) | 53 (68%) | 16.8 [2.9–60.4] | |
unknown | 1 (1%) | 1 (1%) | ||
Overall Survival (10y) | alive | 38 (54%) | 41 (53%) | 13.1 [2.9–60.40] |
dead | 31 (45%) | 36 (46%) | 17.0 [4.5–44.9] | |
unknown | 1 (1%) | 1 (1%) |
Risk Factors | n | 3-Year PFS | 10-Year PFS | |||
---|---|---|---|---|---|---|
p | HR (95% CI) | p | HR (95% CI) | |||
Metastasis | M0 | 34 | 0.467 | 1.7 (0.4–7.7) | 0.351 | 2.0 (0.5–9.0) |
M1 | 10 | |||||
Nodal status | N0 | 16 | 0.858 | 1.1 (0.4–3.2) | 0.819 | 0.9 (0.3–2.4) |
N1 | 28 | |||||
CTC before therapy | negative | 36 | 0.101 | 2.8 (0.8–9.7) | 0.08 | 3.0 (0.9–10.0) |
positive | 8 | |||||
Residual tumor burden | yes | 13 | 0.023 | 2.9 (1.2–7.4) | 0.011 | 3.3 (1.3–8.4) |
no | 31 | |||||
Platinum-based chemotherapy | no resistance | 36 | <0.0001 | 16.4 (4.5–59.2) | <0.0001 | 28.8 (6.4–130.0) |
resistance | 8 | |||||
HLA-GEV status | <18.45 ng/mL | 33 | 0.029 | 2.9 (1.1–7.6) | 0.006 | 3.8 (1.5–9.9) |
>18.45 ng/mL | 11 |
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Schwich, E.; Rebmann, V.; Horn, P.A.; Celik, A.A.; Bade-Döding, C.; Kimmig, R.; Kasimir-Bauer, S.; Buderath, P. Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer. Cancers 2019, 11, 1106. https://doi.org/10.3390/cancers11081106
Schwich E, Rebmann V, Horn PA, Celik AA, Bade-Döding C, Kimmig R, Kasimir-Bauer S, Buderath P. Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer. Cancers. 2019; 11(8):1106. https://doi.org/10.3390/cancers11081106
Chicago/Turabian StyleSchwich, Esther, Vera Rebmann, Peter A. Horn, Alexander A. Celik, Christina Bade-Döding, Rainer Kimmig, Sabine Kasimir-Bauer, and Paul Buderath. 2019. "Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer" Cancers 11, no. 8: 1106. https://doi.org/10.3390/cancers11081106
APA StyleSchwich, E., Rebmann, V., Horn, P. A., Celik, A. A., Bade-Döding, C., Kimmig, R., Kasimir-Bauer, S., & Buderath, P. (2019). Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer. Cancers, 11(8), 1106. https://doi.org/10.3390/cancers11081106