PD-L1 Is Expressed In Ovarian Cancer And Could Be Upregulated By Cisplatin/Clinical Outcome And Prognostic Factors Of Patients With Early-stage Epithelial Ovarian Cancer

Part 1PD-L1 is expressed in ovarian cancer and could be upregulated by cisplatin[Background and Objectives]Programed-death ligand 1 is a hotspot immune check-up point gene and is closely related to tumor immune escape.PD-L1 is mainly expressed in antigen presenting cells which could down-regulate immune function when it is ligated with its receptor PD1 located in T cell.It's reported that PD-L1 is commonly expressed in human tumor tissues and show uncertain clinical prognostic significance.In ovarian cancer patients,PD-L1 protein is found in ascites,peripheral serum as well as tumor tissues.Some author stated that PD-L1 overexpression indicated better clinical outcomes.In this study,we aimed to test the PD-L1 protein expression level in vitro and in vivo via IHC.We also tested the mRNA level of PD-L1 in SKOV3 cell line after cisplatin intervention,trying to explore the effect of chemotherapy on PD-L1 expression.[Materials and Methods]SKOV3 and SKOV3 cisplatin resistant cell line,OVCR-3 and SKOV-3 cisplatin resistant cell line were cultured.PD-L1 protein expression was tested in above cell lines via ICC.PD-L1 protein expression was also measured in 21 ovarian cancer patients and 16 control cases.PD-L1 mRNA expression in SKOV3 cell line was measured by RT-real time PCR to detect the mRNA level changes after cisplatin intervention for 36 hours.[Results]PD-L1 protein membrane staining was detected inSKOV-3,SKOV3 cisplatin resistance cell,OVCR3,and OVCR3 cisplatin resistance cell.Cisplatin could up-regulate PD-L1 mRNA expression in SKOV3 cell line and the effect of up-regulation is dose-dependent.PD-L1 protein level is detected in 56.4%high-grade serous ovarian cancer patients but no normal ovarian patientsand the expression is not related to main clinical factors[Conclusion]PD-L1 protein is expressed in ovarian cancer tumor tissue and cell lines.Cisplatin could upregulate PD-L1 mRNA expression.Part 2Clinical outcome and prognostic factors of patients with early-stage epithelial ovarian cancer.[Background and Objectives]Although the survival rate for patients with early stage ovarian cancer is optimistic,some subsets of patients experienced more recurrences than others.Studies on prognostics factors gave conflicting results.The treatment of early stage ovarian cancer is still controversial.[Materials and Methods]We investigated consecutive 221 patients with stage ?/? ovarian cancer at our institution from 1999 to 2010.Univariate and multivariate analysis of progression free survival(PFS)and overall survival(OS)in relation to various clinical and pathological variables were performed.[Results]After a median follow-up of 79 months,the 5-year/10-year PFS and 5-year/10-year OS were 78%/76%and 90%/87%respectively.Multivariate analysis revealed that stage as the most prominent prognostic factor in terms of PFS(stage ? vs stage ?A vs stage ?B,Hazard Ratio(HR):1 vs 4 vs 6.1)and OS(stage ? vs stage ?,HR:1 vs 2.1).Peritoneal biopsy reduced the risk of recurrence by 29%(95%CI:0.15-0.58).Ascites(HR = 2.8,95%CI:1.2-6.6)and not the first-line chemotherapy(HR = 2.6,95%CI:1.1-6.5)also contributed to decreased OS.[Conclusion]Overall,early-stage ovarian cancer had a favorable prognosis,stage was the most powerful prognostic factor.