| ObjectivesProgrammed death ligand-1(PD-L1)inhibitors have achieved certain success in the treatment of many tumors,but whether they can be effectively applied in the treatment of ovarian cancer has not been determined.Anti-pd-l1 therapy has been observed to be more unstable in patients with ovarian cancer.There is evidence that genomic instability/damage can affect PD-L1 expression,but this relationship in ovarian cancer is unclear.This study intends to prove the relationship between the degree of gene damage in ovarian cancer cells and the expression of PD-L1,so as to provide a feasible basis for the treatment of ovarian cancer through the PD-L1 pathway.MethodsCommercial ovarian cancer TMA samples and non-small cell lung cancer TMA were used as controls.Repair assisted damage detection(RADD)method and modified RADD(oxRADD)method were used to detect DNA damage and oxidative damage in ovarian cancer samples,respectively.The expression of PD-L1 protein in ovarian tumor cells was observed by immunohistochemistry.Laser confocal microscopy was used to image and acquire images of each tissue core in the TMAs.The binary mask of RADD/oxRADD and PD-L1 signal intensity was created,the fluorescence intensity of each core was recorded,and the image data were drawn.Then,the correlation between the degree of DNA damage or oxidative damage of each sample and its PD-L1 protein expression level was analyzed,and the correlation between the two was calculated.ResultsBoth RADD method and the modified oxRADD method can effectively detect the DNA damage level in tumor tissues,among which the improved RADD method has a higher detection level.There is a high incidence of DNA oxidative damage in ovarian tumors.With the increase of DNA oxidative damage level,the expression of PD-L1 in tumors also increased.The most significant differences in DNA damage levels were found between well-differentiated serous tumors and endometrioid tumors compared with normal tissue.Moreover,pD-L1 expression was found to be highly correlated with DNA damage level.When the correlation between more core pathological subtypes was further examined,DNA damage levels detected by oxRADD for both highly differentiated serous and endometrioid lesions showed a good correlation with PD-L1.Among them,the correlation between DNA damage level and PD-L1 expression was highest in ovarian mucinous tumors.ConclusionsThe present study established a link between oxidative DNA damage or genomic instability and PD-L1 expression in different types of ovarian tumors.This provides a possible reference for the treatment of ovarian cancer subtypes with oxidative DNA damage by PD-L1 immunoassay. |
