Objective Ovarian cancer is the gynecologic malignancy with the highest case-fatality rate due to the development of chemotherapy resistance. Predictors of chemotherapy response are needed to guide chemotherapy selection and improve survival for patients with ovarian cancer. Wnt signaling may impact chemoresistance in ovarian cancer.

Methods We studied The Cancer Genome Atlas patients with ovarian cancer treated with intraperitoneal or intravenous-only adjuvant chemotherapy. Cox regression tested associations of expression of 26 Wnt pathway genes with progression-free survival and overall survival. Permutation tests compared survival between chemotherapy groups stratified by expression. P values are two-tailed.

Results Increased FZD3 was associated with increased survival (intraperitoneal group, overall survival: hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.11–0.72, P = 0.009; progression-free survival: HR, 0.58; 95% CI, 0.37–0.92, P = 0.020) (intravenous-only group, overall survival: HR, 0.85; 95% CI, 0.72–0.99, P = 0.039; progression-free survival: HR, 0.83; 95% CI, 0.73–0.95, P = 0.006). Low FZD3 predicted decreased overall survival after intraperitoneal versus intravenous-only chemotherapy (21.7 vs 33.3 months, P < 0.0001). Increased APC2 was associated with decreased overall survival (HR, 1.22; 95% CI, 1.05–1.42; P = 0.009) and progression-free survival (HR, 1.28; 95% CI, 1.12–1.45; P = 0.0002).

Conclusions Up-regulated tumor Wnt signaling predicts increased ovarian cancer survival. FZD3 may predict benefit from intraperitoneal chemotherapy.