Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer
Abstract Background Ovarian cancer has the highest mortality of all gynecological cancers and surgery is commonly used as final diagnostic. Available literature indicates that women with benign tumors could often be conservatively managed, but accurate molecular tests are needed for triaging when go...
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Nature Portfolio
2025-06-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00945-0 |
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| author | Mikaela Moskov Julia Hedlund Lindberg Maria Lycke Emma Ivansson Ulf Gyllensten Karin Sundfeldt Karin Stålberg Stefan Enroth |
| author_facet | Mikaela Moskov Julia Hedlund Lindberg Maria Lycke Emma Ivansson Ulf Gyllensten Karin Sundfeldt Karin Stålberg Stefan Enroth |
| author_sort | Mikaela Moskov |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer has the highest mortality of all gynecological cancers and surgery is commonly used as final diagnostic. Available literature indicates that women with benign tumors could often be conservatively managed, but accurate molecular tests are needed for triaging when gold-standard imaging techniques are inconclusive or lacking. Methods Here, we analyzed 5416 plasma proteins in two independent cohorts (N1 = 171, N2 = 233) with women surgically diagnosed with benign or malignant tumors. Using one cohort as discovery, we compared protein levels of benign tumors with early stage (I–II), late stage (III–IV) or any stage (I–IV) ovarian cancer and trained risk-score reporting multivariate models including a fixed cut-off for malignancy. Associations and model performance was then evaluated in the replication cohort. Results We identify 327 biomarker associations, corresponding to 191 unique proteins, and replicate 326 (99.7%). By comparing the 191 proteins with their corresponding tumor gene expression we find that only 11% (21/191) have significant correlation. Through analyzes of protein-protein correlation networks, we find that 62 of the 191 proteins have high correlation with at least one other protein, suggesting that many of the associations are secondary effects. In the replication cohort, our model has areas under the curve (AUC = 0.96) corresponding to 97% sensitivity at 68% specificity. For early-stage tumors, we estimate the sensitivity to 91% at a specificity of 68% as compared to 85% and 54% for CA-125 alone. Conclusions Our results indicates that up to one third of benign cases can be identified by molecular measures thereby reducing the need for diagnostic surgery. |
| format | Article |
| id | doaj-art-90c5e1e5f05346ed811dfdc55f577ecf |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-90c5e1e5f05346ed811dfdc55f577ecf2025-08-20T02:39:44ZengNature PortfolioCommunications Medicine2730-664X2025-06-015111210.1038/s43856-025-00945-0Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancerMikaela Moskov0Julia Hedlund Lindberg1Maria Lycke2Emma Ivansson3Ulf Gyllensten4Karin Sundfeldt5Karin Stålberg6Stefan Enroth7Department of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala UniversityDepartment of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala UniversityDepartment of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg UniversityDepartment of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala UniversityDepartment of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala UniversityDepartment of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg UniversityDepartment of Women’s and Children’s Health, Uppsala UniversityDepartment of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala UniversityAbstract Background Ovarian cancer has the highest mortality of all gynecological cancers and surgery is commonly used as final diagnostic. Available literature indicates that women with benign tumors could often be conservatively managed, but accurate molecular tests are needed for triaging when gold-standard imaging techniques are inconclusive or lacking. Methods Here, we analyzed 5416 plasma proteins in two independent cohorts (N1 = 171, N2 = 233) with women surgically diagnosed with benign or malignant tumors. Using one cohort as discovery, we compared protein levels of benign tumors with early stage (I–II), late stage (III–IV) or any stage (I–IV) ovarian cancer and trained risk-score reporting multivariate models including a fixed cut-off for malignancy. Associations and model performance was then evaluated in the replication cohort. Results We identify 327 biomarker associations, corresponding to 191 unique proteins, and replicate 326 (99.7%). By comparing the 191 proteins with their corresponding tumor gene expression we find that only 11% (21/191) have significant correlation. Through analyzes of protein-protein correlation networks, we find that 62 of the 191 proteins have high correlation with at least one other protein, suggesting that many of the associations are secondary effects. In the replication cohort, our model has areas under the curve (AUC = 0.96) corresponding to 97% sensitivity at 68% specificity. For early-stage tumors, we estimate the sensitivity to 91% at a specificity of 68% as compared to 85% and 54% for CA-125 alone. Conclusions Our results indicates that up to one third of benign cases can be identified by molecular measures thereby reducing the need for diagnostic surgery.https://doi.org/10.1038/s43856-025-00945-0 |
| spellingShingle | Mikaela Moskov Julia Hedlund Lindberg Maria Lycke Emma Ivansson Ulf Gyllensten Karin Sundfeldt Karin Stålberg Stefan Enroth Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer Communications Medicine |
| title | Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer |
| title_full | Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer |
| title_fullStr | Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer |
| title_full_unstemmed | Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer |
| title_short | Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer |
| title_sort | deep plasma proteomics identifies and validates an eight protein biomarker panel that separate benign from malignant tumors in ovarian cancer |
| url | https://doi.org/10.1038/s43856-025-00945-0 |
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