Figure 1.

Ascites can activate WNT signaling and this activity is associated with worse prognosis. A) A synopsis of the evaluation of 47 OC cell lines used as HGSC tumor models by genomic profiling adapted from ¹⁷. Unlike the most frequently used cell lines (SKOV-3, A2780, OVCAR-3, CAOV-3 and IGROV1), the Kuramochi cell line credibly reflects HGSC both on the genomic and transcriptomic level. The grey panel summarizes the molecular profile of 500 HGSC tumor samples, the green panel summarizes the genetic events typical for HGSC and the red panel summarizes the genetic events typical for OC subtypes other than HGSC. B) Assessment of the WNT signaling induction in Kuramochi cell line. Active WNT signaling results in the phosphorylation-induced electrophoretic shift of DVL proteins. Black triangle - phosphorylated and shifted (PS-) form, open triangle - non-phosphorylated form. The endogenous expression of WNTs and subsequent autocrine stimulation is evidenced by the increase in PS-DVL to total levels of DVL protein in comparison with a control, LGK974 treated cells. Similarly, responsiveness to exogenous WNTs is shown. C) Scheme of the experiment used to assay WNT signaling activity in ascites. D) 54.5% of tested malignant ascites were able to induce WNT signaling in Kuramochi cells. Ascites were subsequently divided into two groups: A - WNT signaling activating ascites and B - WNT signaling non-activating ascites. E) Overall survival of patients in group A and B. F) Comparison of clinical characteristics and disease outcome of patients in groups A and B. G) Progression-free survival of patients in group A and B. Quantification of WBs is available in Supplementary Fig. S1.