Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer
Background: Despite substantial effort, there remains a lack of biomarker-based, clinically relevant testing for the accurate, non-invasive diagnostic or prognostic profiling of epithelial ovarian cancers (EOC). Our previous work demonstrated that whilst the inflammatory marker C-X-C motif chemokine...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/11/6/1048 |
| _version_ | 1797531061900541952 |
|---|---|
| author | Sung-Woog Kang Adam Rainczuk Martin K. Oehler Thomas W. Jobling Magdalena Plebanski Andrew N. Stephens |
| author_facet | Sung-Woog Kang Adam Rainczuk Martin K. Oehler Thomas W. Jobling Magdalena Plebanski Andrew N. Stephens |
| author_sort | Sung-Woog Kang |
| collection | DOAJ |
| description | Background: Despite substantial effort, there remains a lack of biomarker-based, clinically relevant testing for the accurate, non-invasive diagnostic or prognostic profiling of epithelial ovarian cancers (EOC). Our previous work demonstrated that whilst the inflammatory marker C-X-C motif chemokine ligand 10 (CXCL10) has prognostic relevance in ovarian cancer, its use is complicated by the presence of multiple, N-terminally modified variants, mediated by several enzymes including Dipeptidyl Peptidase 4 (DPP4). Methods: In this study, we provide the first evidence for the “Active Ratio Test” (ART) as a novel method to measure biologically relevant CXCL10 proteoforms in clinical samples. Results: In a cohort of 275 patients, ART accurately differentiated patients with malignant EOCs from those with benign gynaecological conditions (AUC 0.8617) and significantly out-performed CA125 alone. Moreover, ART combined with the measurement of CA125 and DPP4 significantly increased prognostic performance (AUC 0.9511; sensitivity 90.0%; specificity 91.7%; Cohen’s d > 1) for EOC detection. Conclusion: Our data demonstrate that ART provides a useful method to accurately discriminate between patients with benign versus malignant EOC, and highlights their relevance to ovarian cancer diagnosis. This marker combination may also be applicable in broader screening applications, to identify or discriminate benign from malignant disease in asymptomatic women. |
| first_indexed | 2024-03-10T10:38:47Z |
| format | Article |
| id | doaj.art-23b809b8fffc472c8fb71a1244e5d58f |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T10:38:47Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-23b809b8fffc472c8fb71a1244e5d58f2023-11-21T23:07:04ZengMDPI AGDiagnostics2075-44182021-06-01116104810.3390/diagnostics11061048Active Ratio Test (ART) as a Novel Diagnostic for Ovarian CancerSung-Woog Kang0Adam Rainczuk1Martin K. Oehler2Thomas W. Jobling3Magdalena Plebanski4Andrew N. Stephens5Hudson Institute of Medical Research, Clayton 3168, AustraliaHudson Institute of Medical Research, Clayton 3168, AustraliaDepartment of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide 5000, AustraliaDepartment of Gynaecology Oncology, Monash Medical Centre, Bentleigh East 3165, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Bundoora 3083, AustraliaHudson Institute of Medical Research, Clayton 3168, AustraliaBackground: Despite substantial effort, there remains a lack of biomarker-based, clinically relevant testing for the accurate, non-invasive diagnostic or prognostic profiling of epithelial ovarian cancers (EOC). Our previous work demonstrated that whilst the inflammatory marker C-X-C motif chemokine ligand 10 (CXCL10) has prognostic relevance in ovarian cancer, its use is complicated by the presence of multiple, N-terminally modified variants, mediated by several enzymes including Dipeptidyl Peptidase 4 (DPP4). Methods: In this study, we provide the first evidence for the “Active Ratio Test” (ART) as a novel method to measure biologically relevant CXCL10 proteoforms in clinical samples. Results: In a cohort of 275 patients, ART accurately differentiated patients with malignant EOCs from those with benign gynaecological conditions (AUC 0.8617) and significantly out-performed CA125 alone. Moreover, ART combined with the measurement of CA125 and DPP4 significantly increased prognostic performance (AUC 0.9511; sensitivity 90.0%; specificity 91.7%; Cohen’s d > 1) for EOC detection. Conclusion: Our data demonstrate that ART provides a useful method to accurately discriminate between patients with benign versus malignant EOC, and highlights their relevance to ovarian cancer diagnosis. This marker combination may also be applicable in broader screening applications, to identify or discriminate benign from malignant disease in asymptomatic women.https://www.mdpi.com/2075-4418/11/6/1048ovarian cancerCXCL10Active Ratio Testbiomarkersearly detectionELISA |
| spellingShingle | Sung-Woog Kang Adam Rainczuk Martin K. Oehler Thomas W. Jobling Magdalena Plebanski Andrew N. Stephens Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer Diagnostics ovarian cancer CXCL10 Active Ratio Test biomarkers early detection ELISA |
| title | Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer |
| title_full | Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer |
| title_fullStr | Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer |
| title_full_unstemmed | Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer |
| title_short | Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer |
| title_sort | active ratio test art as a novel diagnostic for ovarian cancer |
| topic | ovarian cancer CXCL10 Active Ratio Test biomarkers early detection ELISA |
| url | https://www.mdpi.com/2075-4418/11/6/1048 |
| work_keys_str_mv | AT sungwoogkang activeratiotestartasanoveldiagnosticforovariancancer AT adamrainczuk activeratiotestartasanoveldiagnosticforovariancancer AT martinkoehler activeratiotestartasanoveldiagnosticforovariancancer AT thomaswjobling activeratiotestartasanoveldiagnosticforovariancancer AT magdalenaplebanski activeratiotestartasanoveldiagnosticforovariancancer AT andrewnstephens activeratiotestartasanoveldiagnosticforovariancancer |