Study On The Relationship Between Copy Number Variations And The Heterogeneity Of Ovarian Tumors

Background and ObjectivesOvarian cancer has become the gynecological cancer with the highest mortality rate nowadays.Because of its high degree of malignancy,the research into the heterogeneity of ovarian cancer shows its necessity.In recent years,copy number variations have become an important part of the investigation into mechanism of diseases.There are more than 1500 studies between CNVs and common diseases.The aim of this study was to discuss the correlation between copy number variations and the heterogeneity of ovarian tumors and the possible impact on prognosis.MethodsThis is a retrospective trail.Searching the medical charts at Peking Union Medical College Hospital from 2005 to 2015,54 EOC patients with their follow-up were collected.The pathology sections were reviewed by one experienced pathologist.The IHC was carried out on the tissue microarray made of the tumor tissue sampled from FFPE specimen.The digital images were collected and scored by the pathologist,and the scoring is blind randomized.The scores were used to do correlation analysis with clinical information,which mainly contained pathology,the cycles of TC chemotherapy until CA125 return to normal,PFS and OS.The data was analyzed with IBM SPSS Statistics 19.0.Results1.The expression of BRD4 was significantly different between high-grade serous carcinoma(HGSC)and endometriod carcinoma(EC)(p=0.021),HGSC and transitional cell carcinoma(TCC)(p=0.036).The expression of DDB1 was significantly different between clear cell carcinoma(CCC)and low-grade serous carcinoma(LGSC)(p=0.012),LGSC and EC(p=0.015).2.The expression of BRD4,FAK,MARK4 was significantly related to chemosensitivity(p values were 0.028.0.004.0.005).3.The expression of MARK4,BCAT1 was significantly related to PFS(p values were 0.002.0.003).4.The expression of BRD4 was significantly different between the two groups that grouped by an OS of 30 months(p=0.010).The expression of DDB1 was significantly different between the two groups that grouped by an OS of 40 months(p=0.011)and 50 months(p=0.008).Conclusions1.The expression of BRD4 and DDB1 was statistically significant among different pathological types.It is concluded that some CNVs are associated with the pathological types of ovarian tumors,but the molecular mechanism of BRD4 and DDB1 cannot explain this association.2.The expression of BRD4,FAK,MARK4 was significantly related to chemosensitivity and Pearson>0,which indicated that the higher the expression level of these proteins,the lower the sensitivity of the patients to the chemotherapy.3.The expression of MARK4 and BCAT1 was significantly related to PFS,and the expression of BRD4 and DDB1 was significantly related to OS.Among them mARK4,BCAT1 and BRD4 had positive correlation with PFS/OS,while DDB1 had negative correlation with PFS/OS.4.We analyzed the Cutoff values of the IHC scores correlated to the heterogeneity of ovarian cancers mentioned above,and confirmed that in terms of chemosensitivity and PFS,we could find statistically significant Cutoff values,which might help us to judge the IHC staining.5.Some of the CNVs are correlated with the heterogeneity of ovarian tumors,but we cannot confirm whether CNVs can be used as markers of tumor heterogeneity.This study can just provide some clues for further research.