Plasma Concentrations of Matrilysins (MMP-7, MMP-26) and Stromelysins (MMP-3, MMP-10) as Diagnostic Biomarkers in High-Grade Serous Ovarian Cancer Patients
Abstract
1. Introduction
2. Results
2.1. Plasma Levels for Tested Parameters in Serous High-Grade Serous Ovarian Carcinoma Patients and in Control Groups
2.2. Correlation by Spearman’s Method
2.3. Diagnostic Criteria of Tested MMPs: CA 125 and HE-4
2.4. Evaluation of the Diagnostic Power of Tests by ROC Function
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Biochemical Analyses
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
MMP-7 | Metalloproteinase 7 |
MMP-3 | Metalloproteinase 3 |
MMP-10 | Metalloproteinase 10 |
MMP-26 | Metalloproteinase 26 |
CA125 | Cancer antigen 125 |
HE4 | Human epididymis protein 4 |
OC | Ovarian cancer |
BL | Begin lesion |
HW | Healthy women |
MMPs | Matrix metalloproteinases |
ELISA | Enzyme-linked immunosorbent assay |
CMIA | Chemiluminescent Microparticle Immuno Assay |
FIGO | International Federation of Gynecology and Obstetrics |
USG | Medical ultrasound |
SE | Diagnostic sensitivity |
SP | Diagnostic specificity |
PPV | Diagnostic positive predictive value |
NPV | Diagnostic negative predictive value |
ACC | Diagnostic accuracy |
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Tested Parameters | Ovarian Cancer (OC) Stage I–II Median Range 95 Percentile 5 Percentile | Ovarian Cancer (OC) Stage III–IV Median Range 95 Percentile 5 Percentile | Statistical Significance |
---|---|---|---|
MMP-7 [ng/mL] | 4.500 1.800–27.40 24.28 2.002 | 4.800 1.300–25.20 2.200 20.20 | p < 0.0001 |
MMP-26 [pg/mL] | 9240 5850–47,950 44,383 6092 | 9220 3578–47,950 23,455 6175 | p < 0.0001 |
MMP-3 [pg/mL] | 9065 4159–39,441 25,378 4224 | 9328 3033–40,000 34,304 4179 | p = 0.197 |
MMP-10 [ng/mL] | 87.06 38.90–1131 566.3 50.29 | 103.8 33.60–1131 551.4 41.40 | p < 0.0001 |
CA125 [U/mL] | 105.1 17.10–1000 411.6 19.46 | 495.7 23.00–4113 2063 38.82 | p < 0.0001 |
HE4 [U/mL] | 182.4 28.90–1944 1222 36.35 | 140.4 35.57–1500 1500 37.93 | p < 0.0001 |
Parameter | MMP-7 | MMP-26 | MMP-3 | MMP-10 | CA125 | HE4 |
---|---|---|---|---|---|---|
Serous Ovarian Cancer | ||||||
MMP-7 | - | r = −0.2519 p = 0.0119 | r = −0.1741 p = 0.0849 | r = −0.08830 p = 0.3848 | r = 0.02867 p = 0.9775 | r = 0.07760 p = 0.4452 |
MMP-26 | r = 0.02042 p = 0.8107 | - | r = −0.2086 p = 0.0134 | r = −0.2312 p = 0.0060 | r = 0.1725 p = 0.0415 | r = −0.2164 p = 0.0102 |
MMP-3 | r = −0.06679 p = 0.4330 | r = −0.02095 p = 0.8060 | - | r = 0.1963 p = 0.0201 | r = 0.07582 p = 0.3732 | r = 0.04334 p = 0.6112 |
MMP-10 | r = −0.2030 p = 0.0161 | r = 0.2168 p = 0.0101 | r = 0.1963 p = 0.0201 | - | r = 0.07967 p = 0.3494 | r = 0.2131 p = 0.0115 |
Benign lesion | ||||||
MMP-7 | - | r = 0.1666 p = 0.0993 | r = 0.03748 p = 0.7126 | r = −0.1047 p = 0.3025 | r = −0.04681 p = 0.6455 | r = 0.02135 p = 0.8339 |
MMP-26 | r = 0.1666 p = 0.0993 | - | r = 0.126 p =0.952 | r = 0.03624 p = 0.7218 | r = 0.05994 p = 0.9530 | r = −0.1387 p = 0.1709 |
MMP-3 | r = 0.03748 p = 0.7126 | r = 0.05994 p = 0.9530 | - | r = 0.1118 p = 0.2704 | r = 0.04293 p = 0.6731 | r = −0.06714 p = 0.5090 |
MMP-10 | r = −0.1047 p = 0.3025 | r = 0.03624 p = 0.7218 | r = 0.1118 p = 0.2704 | - | r = −0.05854 p = 0.5649 | r = −0.1463 p = 0.1486 |
Healthy women | ||||||
MMP-7 | - | r = 0.1145 p = 0.4284 | r = −0.2479 p = 0.0825 | r = 0.2146 p = 0.1346 | r = 0.2308 p = 0.1069 | r = 0.1665 p = 0.365 |
MMP-26 | r = 0.1145 p = 0.4284 | - | r = 0.07582 p = 0.6007 | r = −0.1023 p = 0.4797 | r = −0.03011 p = 0.9836 | r = 0.07276 p = 0.6193 |
MMP-3 | r = −0.2479 p = 0.0825 | r = 0.07582 p = 0.6007 | - | r = 0.1427 p = 0.3228 | r = 0.03492 p = 0.8098 | r = 0.08869 p = 0.5402 |
MMP-10 | r = 0.2146 p = 0.1346 | r = −0.1023 p = 0.4797 | r = 0.1427 p = 0.3228 | - | r = −0.1389 p = 0.3362 | r = −0.1787 p = 0.2144 |
SE | SP | PPV | NPV | ACC | ||
---|---|---|---|---|---|---|
MMP-3 | value [%] | 64% | 60% | 76.2% | 45.45% | 62.67% |
95 cl [%] | 53.79–73.36% | 45.18–73.59% | 68.85–82.25% | 37.10–54.08% | 54.40–70.42% | |
MMP-7 | value [%] | 94% | 86% | 93.07% | 87.76% | 91.33% |
95 cl [%] | 87.40–97.77% | 73.26–94.18% | 87.09–96.40% | 76.60–94.01% | 85.64–95.30% | |
MMP-10 | value [%] | 81% | 62% | 81% | 62% | 74.67% |
95 cl [%] | 71.93–88.16% | 47.17–75.35% | 74.71–86.02% | 50.76–72.09% | 66.93–81.41% | |
MMP-26 | value [%] | 82% | 60% | 80.39% | 62.5% | 74.67% |
95 cl [%] | 73.05–88.97% | 45.18–73.59% | 74.26–85.35% | 50.88–72.84% | 66.93–81.41% | |
CA125 | value [%] | 93% | 98% | 98.94% | 87.5% | 94.67% |
95 cl [%] | 86.11–97.14% | 89.35–99.95% | 93.03–99.85% | 77.39–93.47% | 89.76–97.67% | |
HE-4 | value [%] | 75% | 94% | 96.15% | 65.28% | 81.33% |
95 cl [%] | 65.34–83.12% | 83.45–98.75% | 89.24–98.69% | 57.07–72.67% | 74.16–87.22% |
Stage I–II | ||||||
---|---|---|---|---|---|---|
SE | SP | PPV | NPV | ACC | ||
MMP-3 | value [%] | 58.33% | 60.00% | 41.18% | 75.00% | 59.46% |
95 cl [%] | 36.64–77.89% | 45.18–73.59% | 30.24–53.06% | 63.97–83.53% | 47.41–70.73% | |
MMP-7 | value [%] | 91.67% | 86.00% | 75.86% | 95.56% | 87.84% |
95 cl [%] | 73.00–98.97% | 73.26–94.18% | 61.01–86.33% | 85.02–98.79% | 78.16–94.29% | |
MMP-10 | value [%] | 91.67% | 62.00% | 53.66% | 93.94% | 71.62% |
95 cl [%] | 73.00–98.97% | 47.17–75.35% | 44.34–62.73% | 80.16–98.35% | 59.95–81.50% | |
MMP-26 | value [%] | 75.00% | 60.00% | 47.37% | 83.33% | 64.86% |
95 cl [%] | 53.29–90.23% | 45.18–73.59% | 37.38–57.57% | 70.69–91.20% | 52.89–75.61% | |
CA125 | value [%] | 83.33% | 98.00% | 95.24% | 92.45% | 93.24% |
95 cl [%] | 62.62–95.26% | 89.35–99.95% | 74.02–99.29% | 83.34–96.77% | 84.93–97.77% | |
HE-4 | value [%] | 83.33% | 94.00% | 86.96% | 92.16% | 92.16% |
95 cl [%] | 62.62–95.26% | 83.45–98.75% | 68.69–95.30% | 82.73–96.65% | 81.48–96.11% |
Stage III–IV | ||||||
---|---|---|---|---|---|---|
SE | SP | PPV | NPV | ACC | ||
MMP-3 | value [%] | 66.22% | 60.00% | 71.01% | 54.55% | 63.71% |
95 cl [%] | 54.28–76.81% | 45.18–73.59% | 62.71–78.12% | 44.80–63.96% | 54.60–72.15% | |
MMP-7 | value [%] | 96.00% | 86.00% | 91.14% | 93.48% | 92.00% |
95 cl [%] | 88.75–99.17% | 73.26–94.18% | 83.78–95.34% | 82.47–97.76% | 85.78–96.10% | |
MMP-10 | value [%] | 78.67% | 60.00% | 74.68% | 65.22% | 71.20% |
95 cl [%] | 67.68–87.29% | 45.18–73.59% | 67.31–80.86% | 53.46–75.37% | 62.42–78.95% | |
MMP-26 | value [%] | 85.33% | 60.00% | 76.19% | 73.17% | 75.20% |
95 cl [%] | 75.27–92.44% | 45.18–73.59% | 69.23–81.99% | 60.16–83.12% | 66.68–82.49% | |
CA125 | value [%] | 97.33% | 98.00% | 98.65% | 96.08% | 97.60% |
95 cl [%] | 90.70–99.68% | 89.35–99.95% | 91.29–99.80% | 86.19–98.97% | 93.15–99.50% | |
HE-4 | value [%] | 73.33% | 94.00% | 94.83% | 70.15% | 81.60% |
95 cl [%] | 61.86–82.89% | 83.45–98.75% | 85.85–98.23% | 61.60–77.49% | 73.68–87.96% |
Parameters | AUC | SEAUC | 95% CI | p (AUC = 0.5) |
---|---|---|---|---|
MMP-7 | 0.9566 | 0.01756 | 0.9222–0.9911 | <0.0001 |
MMP-26 | 0.7550 | 0.04279 | 0.6711–0.8389 | <0.0001 |
MMP-3 | 0.5821 | 0.04903 | 0.4860–0.6783 | 0.08502 |
MMP-10 | 0.7939 | 0.03749 | 0.7204–0.8673 | <0.0001 |
CA125 | 0.9840 | 0.006660 | 0.9709–0.9971 | <0.0001 |
HE4 | 0.9136 | 0.01971 | 0.8749–0.9522 | <0.0001 |
Stage I–II | ||||
---|---|---|---|---|
Parameters | AUC | SEAUC | 95% CI | p (AUC = 0.5) |
MMP-7 | 0.9548 | 0.01942 | 0.9167–0.9928 | <0.0001 |
MMP-26 | 0.7555 | 0.04967 | 0.6581–0.8528 | <0.0001 |
MMP-3 | 0.5004 | 0.05920 | 0.3844–0.6165 | 0.9943 |
MMP-10 | 0.7939 | 0.03749 | 0.7204–0.8673 | <0.0001 |
CA125 | 0.9840 | 0.006660 | 0.9709–0.9971 | <0.0001 |
HE4 | 0.9179 | 0.03020 | 0.8587–0.9772 | <0.0001 |
Stage III–IV | ||||
Parameters | AUC | SEAUC | 95% CI | p (AUC = 0.5) |
MMP-7 | 0.9574 | 0.01791 | 0.9223–0.9926 | <0.0001 |
MMP-26 | 0.7548 | 0.04513 | 0.6663–0.8433 | <0.0001 |
MMP-3 | 0.5865 | 0.05051 | 0.4875–0.6855 | 0.08568 |
MMP-10 | 0.8065 | 0.03683 | 0.7343–0.8787 | <0.0001 |
CA125 | 0.9955 | 0.003221 | 0.9892–1.002 | <0.0001 |
HE4 | 0.6843 | 0.03817 | 0.6095–0.7591 | <0.0001 |
Studied Group | Number of Patients | Age (Median) (Range) | Group Size | ||
---|---|---|---|---|---|
Premenopausal | Postmenopausal | ||||
High-Grade Serous Ovarian Carcinoma in total | High-Grade Serous Ovarian Carcinoma in total | 100 | 60 26–91 | 22 | 78 |
Stage I | 7 | 51 26–70 | 4 | 3 | |
Stage II | 17 | 46 36–74 | 9 | 8 | |
Stage I–II | 24 | 48 26–74 | 13 | 11 | |
Stage III | 38 | 61 36–91 | 4 | 34 | |
Stage IV | 38 | 64 34–80 | 5 | 33 | |
Stage III–IV | 76 | 63 34–91 | 9 | 67 | |
Control groups | Benign ovarian tumour (cystis serous) | 73 | 48 25–80 | 37 | 36 |
Healthy women | 50 | 47 32–69 | 24 | 26 |
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Ewa, G.; Ławicki, P.; Grabowska, H.; Ławicki, M.; Kulesza, M.; Kicman, A.; Malinowski, P.; Ławicki, S. Plasma Concentrations of Matrilysins (MMP-7, MMP-26) and Stromelysins (MMP-3, MMP-10) as Diagnostic Biomarkers in High-Grade Serous Ovarian Cancer Patients. Int. J. Mol. Sci. 2025, 26, 5661. https://doi.org/10.3390/ijms26125661
Ewa G, Ławicki P, Grabowska H, Ławicki M, Kulesza M, Kicman A, Malinowski P, Ławicki S. Plasma Concentrations of Matrilysins (MMP-7, MMP-26) and Stromelysins (MMP-3, MMP-10) as Diagnostic Biomarkers in High-Grade Serous Ovarian Cancer Patients. International Journal of Molecular Sciences. 2025; 26(12):5661. https://doi.org/10.3390/ijms26125661
Chicago/Turabian StyleEwa, Gacuta, Paweł Ławicki, Hanna Grabowska, Michał Ławicki, Monika Kulesza, Aleksandra Kicman, Paweł Malinowski, and Sławomir Ławicki. 2025. "Plasma Concentrations of Matrilysins (MMP-7, MMP-26) and Stromelysins (MMP-3, MMP-10) as Diagnostic Biomarkers in High-Grade Serous Ovarian Cancer Patients" International Journal of Molecular Sciences 26, no. 12: 5661. https://doi.org/10.3390/ijms26125661
APA StyleEwa, G., Ławicki, P., Grabowska, H., Ławicki, M., Kulesza, M., Kicman, A., Malinowski, P., & Ławicki, S. (2025). Plasma Concentrations of Matrilysins (MMP-7, MMP-26) and Stromelysins (MMP-3, MMP-10) as Diagnostic Biomarkers in High-Grade Serous Ovarian Cancer Patients. International Journal of Molecular Sciences, 26(12), 5661. https://doi.org/10.3390/ijms26125661