1. : 1.Introduction The cold shock “Y-box binding protein-1” (YB-1) has an important role in regulation of cellular proliferation and differentiation. Overexpression occurs in various tumor cells and immunohistochemical YB-1 detection serves as marker for tumor aggressiveness and poor clinical prognosis. Given the existence of extracellular YB-1 we set out to determine the diagnostic, predictive and prognostic role of serum YB- 1/p18 for ovarian cancer patients. 2. Methods Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center (CCCC), Charité Medical University, Augustenburger Platz 1, 13353 Berlin, Germany. e-mail: Irena.Rohr@charite.de and Elena.Braicu@charite.de Y-box protein-1/ p18 as novel serum marker for ovarian cancer diagnosis: A study by the Tumor Bank Ovarian Cancer (TOC) 3. Results Fig 1: 1 Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Medical University, Berlin, Germany; ²Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany; 3 Alice Salomon University of Applied Sciences, Berlin; 4 Experimental and Clinical Research Center, a joint cooperation between the Max-Delbruck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany; 5 CellTrend, Luckenwalde, Germany, 6 Clinic for Urology, Otto-von-Guericke University, Magdeburg, Germany Protein fragment YB-1/p18 was quantified by sandwich ELISA (combination of monoclonal and polyclonal antibodies) in serum samples from 132 healthy female volunteers and 206 patients with primary EOC. The ELISA sensitivity and specificity were calculated using receiver operating curves. Correlations of YB-1/p18 expression with age, volume of ascites, and CA125 expression were evaluated using Spearman rank correlation or Kendall´s tau b. Mann-Whitney U test or Kruskal-Wallis H test were used for the association between YB-1/p18 and FIGO stage, histology, grading, residual tumor mass and response to carboplatin. Survival data were calculated using Kaplan Maier curves. 4. Conclusions: An ELISA developed for the detection of fragment p18 derived from cold shock protein YB-1 is suited for (early) EOC diagnosis. Contrary to the hypothesis of elevated YB-1/p18 serum levels in cancer patients reduced levels were found in the cancer cohort, which may be explained by protein multimerization. The ELISA detected lower levels of YB-1/p18 in ovarian cancer patients compared to healthy controls. When a cut-off value of 2,11 U/ml was used the sensitivity was 76% and the specificity 75,8%. p= 0,000 Fig 2: The ELISA detected lower levels of YB-1/p18 in ovarian cancer patients compared to healthy controls. Median (Q 1 -Q 3 ) Age (years)60 (51-67) Overall Survival (months) 31 (13-53) N% Histology Serous19494,2 Endometrioid10,5 Mixed10,5 Clear cell10,5 Undifferentiated21,0 Others31,5 Missing data41,8 FIGO Stage FIGO I62,9 FIGO II125.8 FIGO III13565,5 FIGO IV4823,3 Missing data52,5 Grading Grading I83,9 Grading II5124,8 Grading III14570,4 Missing data20,9 Volume of ascites No ascites5124,8 Ascites <=500ml7837,9 Ascites >500ml7636,9 Missing data10,4 Residual tumor mass None10751,9 < 0.5cm3818,4 < 1cm3014,6 < 2cm62,9 > 2 cm2311,2 Missing data21,0 Response to platinum-based chemotherapy Platinum sensitive 10852,4 Platinum resistant 5225,2 No Chemotherapy31,5 Missing data157,3 Table 1. Patient and tumor characteristics at the time of diagnosis and response to platinum-based chemotherapy. YB-1/p18Median (IQR); N p Histology Serous1.75 (0.61); n=192 0.46 t-test non-serous1.69 (0.88); n=8 FIGO Stage IC – IIC1.79 (0.77); n=18 0.67 t-test IIIA – IV1.74 (0.62); n=181 Grading Grading I1.76 (0.66); n=8 0.124 H-test Grading II1.64 (0.84); n=50 Grading III1.79 (0.49); n=144 Volume of ascites 0 1.79 (0.65); n=51 0.84 H-test <=500ml 1.79 (0.84); n=77 > 500ml 1.7 (0.46); n=75 Residual tumor mass No residual tumor mass 1.75 (0.74); n=106 0.75 H-test < 0,5 cm1.86 (0.55); n=37 < 1 cm1.89 (0.59); n=30 < 2 cm1.92 (0.64); n=6 > 2 cm1.67 (0.47); n=23 Response to platinum-based chemotherapy Platinum sensitive1.73 (0.59); n=106 0.34 t-test Platinum resistant1.67 (0.7); n=52 CA125rho=-0.007 ; n=192 0.92 Agerho=0,162 ; n=2040.021 YB-1/p18 Figure 3. YB-1/p18 serum levels determined by immunoassay in EOC patients (n=206 ) and controls (n=132 ). Table 2: YB-1/p18 characteristics in serum samples from ovarian cancer patients I. Rohr 1*, E. Braicu 1*, J. SehouIi 1, R. Richter 1, M. Heinrich 3, MZ. Muallem 1,R. Dechend 4, H. Heidecke 5, M. Schostak 6, D. Schindele 6, B. Jandrik 6, B. Jandrig 6, X. Gorny², A. En-Nia², J. Lindquist², P.R. Mertens² * Equal contribution