Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer
Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/9/2519 |
| _version_ | 1797554563524329472 |
|---|---|
| author | Sabine Kasimir-Bauer Joanna Roder Eva Obermayr Sven Mahner Ignace Vergote Liselore Loverix Elena Braicu Jalid Sehouli Nicole Concin Rainer Kimmig Lelia Net Heinrich Roder Robert Zeillinger Stefanie Aust on behalf of the OVCAD (Ovarian Cancer Diagnosis initiative) |
| author_facet | Sabine Kasimir-Bauer Joanna Roder Eva Obermayr Sven Mahner Ignace Vergote Liselore Loverix Elena Braicu Jalid Sehouli Nicole Concin Rainer Kimmig Lelia Net Heinrich Roder Robert Zeillinger Stefanie Aust on behalf of the OVCAD (Ovarian Cancer Diagnosis initiative) |
| author_sort | Sabine Kasimir-Bauer |
| collection | DOAJ |
| description | Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method of mass spectrometry, we developed and independently validated (development cohort: <i>n</i> = 199, validation cohort: <i>n</i> = 135) a blood-based proteomic classifier, stratifying EOC patients into good and poor survival groups. We also determined an age dependency of the prognostic performance of this classifier, and our protein set enrichment analysis showed that the good and poor proteomic phenotypes were associated with, respectively, lower and higher levels of complement activation, inflammatory response, and acute phase reactants. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response in a subset of ovarian cancer patients and could therefore be integrated into future processes of therapy planning. |
| first_indexed | 2024-03-10T16:33:56Z |
| format | Article |
| id | doaj.art-6c763c2ff4b74ab1af32c5d51778445b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:33:56Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6c763c2ff4b74ab1af32c5d51778445b2023-11-20T12:38:27ZengMDPI AGCancers2072-66942020-09-01129251910.3390/cancers12092519Definition and Independent Validation of a Proteomic-Classifier in Ovarian CancerSabine Kasimir-Bauer0Joanna Roder1Eva Obermayr2Sven Mahner3Ignace Vergote4Liselore Loverix5Elena Braicu6Jalid Sehouli7Nicole Concin8Rainer Kimmig9Lelia Net10Heinrich Roder11Robert Zeillinger12Stefanie Aust13on behalf of the OVCAD (Ovarian Cancer Diagnosis initiative)Department of Gynecology and Obstetrics, University Hospital of Essen, Hufelandstr. 55, 45147 Essen, GermanyBiodesix, 2970 Wilderness Place #100, Boulder, CO 80301, USADepartment of Obstetrics and Gynecology, Medical University of Vienna, Molecular Oncology Group, Gynecologic Cancer Unit, Comprehensive Cancer Center, 1090 Vienna, AustriaDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Gynecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, B-3000 Leuven, BelgiumDepartment of Gynecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, B-3000 Leuven, BelgiumDepartment of Gynecology, Charité University Medicine, Campus Virchow, 13353 Berlin, GermanyDepartment of Gynecology, Charité University Medicine, Campus Virchow, 13353 Berlin, GermanyDepartment of Gynecology and Obstetrics, Innsbruck Medical University, 6020 Innsbruck, AustriaDepartment of Gynecology and Obstetrics, University Hospital of Essen, Hufelandstr. 55, 45147 Essen, GermanyBiodesix, 2970 Wilderness Place #100, Boulder, CO 80301, USABiodesix, 2970 Wilderness Place #100, Boulder, CO 80301, USADepartment of Obstetrics and Gynecology, Medical University of Vienna, Molecular Oncology Group, Gynecologic Cancer Unit, Comprehensive Cancer Center, 1090 Vienna, AustriaDepartment of Obstetrics and Gynecology, Medical University of Vienna, Molecular Oncology Group, Gynecologic Cancer Unit, Comprehensive Cancer Center, 1090 Vienna, AustriaMass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method of mass spectrometry, we developed and independently validated (development cohort: <i>n</i> = 199, validation cohort: <i>n</i> = 135) a blood-based proteomic classifier, stratifying EOC patients into good and poor survival groups. We also determined an age dependency of the prognostic performance of this classifier, and our protein set enrichment analysis showed that the good and poor proteomic phenotypes were associated with, respectively, lower and higher levels of complement activation, inflammatory response, and acute phase reactants. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response in a subset of ovarian cancer patients and could therefore be integrated into future processes of therapy planning.https://www.mdpi.com/2072-6694/12/9/2519ovarian cancerproteomicsmass spectrometrysurvival |
| spellingShingle | Sabine Kasimir-Bauer Joanna Roder Eva Obermayr Sven Mahner Ignace Vergote Liselore Loverix Elena Braicu Jalid Sehouli Nicole Concin Rainer Kimmig Lelia Net Heinrich Roder Robert Zeillinger Stefanie Aust on behalf of the OVCAD (Ovarian Cancer Diagnosis initiative) Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer Cancers ovarian cancer proteomics mass spectrometry survival |
| title | Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer |
| title_full | Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer |
| title_fullStr | Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer |
| title_full_unstemmed | Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer |
| title_short | Definition and Independent Validation of a Proteomic-Classifier in Ovarian Cancer |
| title_sort | definition and independent validation of a proteomic classifier in ovarian cancer |
| topic | ovarian cancer proteomics mass spectrometry survival |
| url | https://www.mdpi.com/2072-6694/12/9/2519 |
| work_keys_str_mv | AT sabinekasimirbauer definitionandindependentvalidationofaproteomicclassifierinovariancancer AT joannaroder definitionandindependentvalidationofaproteomicclassifierinovariancancer AT evaobermayr definitionandindependentvalidationofaproteomicclassifierinovariancancer AT svenmahner definitionandindependentvalidationofaproteomicclassifierinovariancancer AT ignacevergote definitionandindependentvalidationofaproteomicclassifierinovariancancer AT liseloreloverix definitionandindependentvalidationofaproteomicclassifierinovariancancer AT elenabraicu definitionandindependentvalidationofaproteomicclassifierinovariancancer AT jalidsehouli definitionandindependentvalidationofaproteomicclassifierinovariancancer AT nicoleconcin definitionandindependentvalidationofaproteomicclassifierinovariancancer AT rainerkimmig definitionandindependentvalidationofaproteomicclassifierinovariancancer AT lelianet definitionandindependentvalidationofaproteomicclassifierinovariancancer AT heinrichroder definitionandindependentvalidationofaproteomicclassifierinovariancancer AT robertzeillinger definitionandindependentvalidationofaproteomicclassifierinovariancancer AT stefanieaust definitionandindependentvalidationofaproteomicclassifierinovariancancer AT onbehalfoftheovcadovariancancerdiagnosisinitiative definitionandindependentvalidationofaproteomicclassifierinovariancancer |