Abstract 452: MIC-1 and Endoglin are protein serum biomarkers capable of increasing the clinical diagnostic specificity of the PSA test
Authors: Kagohara Luciane T. , Li Ji , Pavlovich Christian P. , Davis Christine , Mangold Leslie , Zhu Guangjing , Morrissey Colm , Partin Alan W. , Mandecki Wlodeck , Veltri Robert W. 
Published: July 2016

Abstract
PSA test and digital rectal examination have been routinely used to screen for prostate cancer (PCa). PSA screening revolutionized the management of PCa, especially with regards to early detection. Before the PSA test was available, ∼20% of men were diagnosed with PCa that had already spread to the bone. Today, that number is around 4%. However, it is estimated that 56% of the cases are overdiagnosed resulting in overtreatment and exposing the patients to serious unnecessary treatment morbidities. Also the rate of false-positives is incredibly high (60-80%), since PSA is not cancer specific. It is critical to discriminate clinically significant PCa patients requiring definitive treatment from those who would safely undergo active surveillance monitoring.
The aim of this project is to identify and incorporate multiple serum protein biomarkers into an assay that will enhance the clinical diagnostic specificity of the PSA screening test. Using ELISA, we analyzed protein serum levels of Endoglin, IL-8 and MIC-1 in samples obtained from 50 PCa patients and 50 non-cancer individuals. ROC curve analysis was used to determine if these biomarkers were capable of separating the 2 groups. Multivariate logistic regression (MLR) was used to identify a panel of biomarkers that combined to PSA would increase the test specificity.
MIC-1 was the only biomarker capable of discriminating PCa from normal cases (AUC = 0.76; p&lt;0.0001). Endoglin protein levels were significantly different (p = 0.0010) between the groups, although the AUC was borderline (AUC = 0.69) to our cut-off (AUC&gt;0.7) it suggests a good potential for this protein as a biomarker in PCa diagnosis. IL-8 did not show significant differences (p = 0.1828) in the levels detected between cancer and normal samples. The expression of these proteins were also evaluated for their prognostic association with clinical-pathological features: Gleason Score (GS), T and N stage. MIC-1 protein levels was capable to separate GS 3+3 and 3+4 from those 4+3 or higher (AUC = 0.73), suggesting that this biomarker might be associated with more aggressive cases. Using MLR, we identified Endoglin, MIC-1 and PSA as a multiple biomarker panel that enhanced specificity of the PSA screening test. The panel resulted in an assay with 88% specificity and 86% sensitivity that is slightly higher than PSA alone (82% specificity; 84% sensitivity). Our results suggest that MIC-1 is a strong candidate as a biomarker for cancer screening and disease aggressiveness. We also showed that when PSA test is combined with the presence of MIC-1 and Endoglin in serum, it resulted in an assay with higher specificity and sensitivity than when these biomarkers are evaluated alone. To validate these results, protein serum levels of Endoglin, MIC-1 and IL-8 will be determined in a bigger cohort of normal and PCa patients. Other biomarkers are also being evaluated.
Citation Format: Luciane T. Kagohara, Ji Li, Christian P. Pavlovich, Christine Davis, Leslie Mangold, Guangjing Zhu, Colm Morrissey, Alan W. Partin, Wlodeck Mandecki, Robert W. Veltri. MIC-1 and Endoglin are protein serum biomarkers capable of increasing the clinical diagnostic specificity of the PSA test. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 452.