The Significance Of Combined Expression Of PD-L1,PARP1 And VEGF In Targeted Therapy Of Ovarian Clear Cell Carcinoma

Objective:PD-L1,PARP1 and VEGF are capable of promoting tumor cell survival,and inhibiting their expressions and functions exerts tumor-suppressor effect.This study aims to explore the therapeutic potential of a combined blocking therapy targeting PD-L1,PARP1,and VEGF in ovarian clear cell carcinoma(OCCC)by analyzing the combined expressions of them.Methods:A total of 80 OCCC specimens,70 high grade serous ovarian cancer(HGSOC)specimens,20 normal ovarian specimens and 20 normal fallopian tube specimens being surgically resected,fixed in formalin and paraffine embedded in the Affiliated Hospital of Qingdao University from January 2014 to December 2018 were collected.Positive expressions of PD-L1,PARP1 and VEGF in collected specimens were measured by immunohistochemical staining.The correlation between relative levels of PD-L1,PARP1 and VEGF,and pathological characteristics and prognosis of OCCC was then analyzed.Moreover,the combined expressions of them were examined.The m RNA level of PD-L1 in ES-2 cells induced with the PARP inhibitor was detected by q RT-PCR.At last,the possibility of OCCC benefiting from the combined blocking therapy of PD-L1,PARP1,and VEGF was investigated.Results:1.PD-L1 and VEGF expressions were significantly higher in OCCC specimens than that of normal tissue specimens(P<0.05).PAPR1 expression was higher in OCCC specimens than that of normal ones as well,although the difference was not statistically significant(75.3% vs.60%,P>0.05).Compared with HGSOC specimens,the ratio of positive expression of PD-L1(47.5% vs.42.8%)was higher in OCCC specimens,while those of PARP1(60% vs.75.7%)and VEGF(52.5% vs.62.9%)were lower,and all of their differences were not statistically significant(P>0.05).2.High expression of PD-L1 was significantly correlated to the FIGO staging(III and IV),omental metastasis,lymph node metastasis and chemotherapy resistance of OCCC(P<0.05),while it was not correlated to the tumor size and ascites formation(P>0.05).High expression of PARP1 was significantly correlated to the ascites formation of OCCC(P<0.05),while it was not correlated to the tumor size,lymph node metastasis,omental metastasis,FIGO staging and chemotherapy response(P>0.05).In addition,high expression of VEGF was significantly correlated to the ascites formation,lymph node metastasis,omental metastasis,FIGO staging and chemotherapy resistance of OCCC(P<0.05).3.Among 80 OCCC specimens detected with positive expressions of PD-L1,PARP1 and VEGF,there were 42(52.5%)with high expressions of 2-3 markers,11(13.75%)with the high expression of PD-L1 only,17(21.25%)with the high expression of PARP1 only,and 10(12.5%)with low expressions of all the 3 markers.4.The protein level of PD-L1 was significantly negatively correlated to that of PARP1 in OCCC specimens(P=0.003,r=-0.347).The m RNA level of PD-L1 was upregulated in PARPi-induced ES-2 cells in the dose-dependent and time-dependent manner.Conclusion:1.PD-L1,PARP1,and VEGF are highly expressed in OCCC to varying degrees.Highly expressed PD-L1,PARP1,and VEGF have a correlation with pathological characteristics and prognosis of OCCC.It is indicated that PD-L1 PARP1,VEGF may of great significance in the progression of OCCC,and they can be utilized as potential therapeutic targets for OCCC.2.PD-L1,PARP1,and VEGF have a high combined expression rate in OCCC,and the expression of PD-L1 is negatively correlated to that of PARP1.The application of PARPi can upregulate PD-L1 in OCCC cell lines.It is indicated that OCCC patients can be benefited from the combined blocking therapy of PD-L1,PARP1,and VEGF.