Background: Ovarian cancer (OvCa) is the most lethal gynecological malignancy. Our integrated -omics approach to OvCa biomarker discovery has identified kallikrein 6 (KLK6) and folate-receptor 1 (FOLR1) as promising candidates but these markers require further validation. Methods: KLK6, FOLR1 CA125 and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls and 216 OvCa patients. The serum biomarker levels were determined by ELISA or automated immunoassay. Results: All biomarkers demonstrated elevations in the sera of OvCa patients compared to controls (p<0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify OvCa patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. As well, the combination of HE4 and FOLR1 was a strong predictor of OvCa diagnosis, displaying comparable sensitivity (65%) to the best performing CA125-based models (67%) at a set specificity of 95%. Conclusions: The markers identified through our integrated -omics approach performed similarly to the clinically-approved markers CA125 and HE4. Furthermore, HE4 represents a powerful diagnostic marker for OvCa and should be used more routinely in a clinical setting. Impact: The implications of our study are two-fold: (1) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (2) we have demonstrated the clinical utility of our integrated -omics approach to identifying novel serum markers with comparable performance to clinical markers.
- Received December 21, 2015.
- Revision received May 13, 2016.
- Accepted May 16, 2016.
- Copyright ©2016, American Association for Cancer Research.