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An Improved Prediction Model for Ovarian Cancer Using Urinary Biomarkers and a Novel Validation Strategy
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 19, p 4938 (2019), Volume 20, Issue 19
- Publication Year :
- 2019
- Publisher :
- MDPI, 2019.
-
Abstract
- This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples with OC (mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772&ndash<br />0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714&ndash<br />0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool.
- Subjects :
- 0301 basic medicine
Urine
Benign tumor
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Carcinoembryonic antigen
urinary biomarker
Prealbumin
lcsh:QH301-705.5
Spectroscopy
Ovarian Neoplasms
biology
General Medicine
Middle Aged
Computer Science Applications
prediction model
ovarian cancer
030220 oncology & carcinogenesis
Biomarker (medicine)
Female
Adult
medicine.medical_specialty
Urinary system
Urology
Vascular Cell Adhesion Molecule-1
Malignancy
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
WAP Four-Disulfide Core Domain Protein 2
medicine
Biomarkers, Tumor
Humans
Physical and Theoretical Chemistry
Molecular Biology
Aged
Creatinine
Models, Statistical
business.industry
Organic Chemistry
medicine.disease
030104 developmental biology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Ovarian cancer
business
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 20
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....6434d9112b2a42b53d6a091c0e48f0f1