Urinary-based detection of MSL, HE4, and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.

person Pauline Wimberger University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany info_outline Pauline Wimberger, Franziska Maria Schwarz, Daniel Klotz, Jan Dominik Kuhlmann

Authors person Pauline Wimberger University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany info_outline Pauline Wimberger, Franziska Maria Schwarz, Daniel Klotz, Jan Dominik Kuhlmann Organizations University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany, TU Dresden, Dresden, Germany, Department of Gynecology and Obstetrics, TU Dresden, Dresden, Germany Abstract Disclosures Research Funding Fujirebio Europe, Gent, Belgium Background: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified by Lumipulse G chemiluminescent enzyme immunoassay (Fujirebio). In total, this study was based on 1080 biomarker detection runs from 188 serum and 172 urine samples from 192 ovarian cancer patients. Results: While absolute concentrations of MSL and CA125 were higher in serum than in urine, serum HE4 concentrations were considerably lower than urinary HE4 concentrations. Nonetheless, relative intra-patient levels of all three biomarkers strongly correlated between matched serum vs. urinary samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity in predicting surgical outcome and relapse/death among both body fluid types (urinary HE4: AUC=0.854; AUC=0.750, respectively). All clinically relevant findings of urinary MSL, HE4 and CA125 were reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis. Conclusions: We report that the capacity of MSL, HE4 and CA125 for predicting surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer.