Hsa_circ₀013958 In The Diagnosis Of Ovarian Cancer And Its Effect On Its Biological Behavior

Objective: Ovarian cancer is one of the common malignant tumors of the female reproductive system,and the mortality rate ranks first in gynecological tumors.A large part is that the symptoms of early ovarian cancer are very hidden,and there are no early diagnostic markers.When the diagnosis is confirmed,it has progressed to advanced ovarian cancer,and the prognosis is not ideal and easy to relapse.The current treatment plan for ovarian cancer is mainly tumor reduction surgery plus neoadjuvant chemotherapy,but the efficacy is still not ideal,and it is easy to produce chemotherapy resistance.Therefore,the exploration of early ovarian cancer diagnostic markers and therapeutic targets has become an important issue to be solved urgently.CircRNA is a new type of non-coding RNA that was first discovered in RNA viruses.Due to its good stability and specificity,it has gradually become a popular research direction.Therefore,exploring circRNA has important clinical significance for tumor occurrence,development and potential molecular mechanism research.Hsa_circ₀013958 is located on chromosome 1 and has a genome length of 816,which is connected by exons 12-14 to form a loop.At present,it is only reported as a sponge of miRNA-134 in non-small cell lung cancer.This study uses hsa_circ₀013958 as the main research object to discuss its diagnostic value for ovarian cancer and its effect on ovarian cancer biological behavior for the first time.Provides new ideas.Method : The expression of hsa_circ₀013958 in normal ovarian epithelial cells,ovarian cancer cells,drug-resistant cells,45 normal ovarian tissues and 45 ovarian cancer tissues were detected by qRT-PCR method.Draw a ROC curve to evaluate the diagnostic efficacy of hsa_circ₀013958 for ovarian cancer,and calculate the approximate index,sensitivity and specificity of its optimal cut-off value.Chi-square test and FISH exact test were used to analyze the relationship between hsa_circ₀013958 and clinical pathological and biological behaviors of ovarian cancer patients.Silence hsa_circ₀013958 in ovarian cancer cells,using the CCK8 experiment to detect its effect on the proliferation of ovarian cancer cells.Transwell test was used todetect its effect on ovarian cancer cell migration and invasion,and flow cytometry was used to detect its effect on ovarian cancer cell apoptosis.Western Blot test was used to detect the changes of epithelial-mesenchymal transition related proteins（E-cadherin and Vimentin）and apoptosis-related proteins（Bax and Bcl-2）in ovarian cancer.Result:The expression of hsa_circ₀013958 in ovarian cancer cells（SKOV3,A2780,OVCAR-3）was significantly higher than that of normal ovarian epithelial cells（P<0.05）.The expression of hsa_circ₀013958 was not significantly different between ovarian cancer cell SKOV3 and ovarian cancer paclitaxel-resistant cell SKOV3-TR30（P> 0.05）.The expression level of hsa_circ₀013958 in ovarian cancer tissue was also significantly higher than that in normal ovarian tissue（P <0.01）,and there was no significant difference between ovarian cancer drug resistance and sensitive tissues（P>0.05）.The area under the ROC curve was 0.912（95% CI = 0.854-0.969,P <0.01）.When the optimal cut-off value is 7.6435,the Youden index is 0.711,the sensitivity is0.800,and the specificity is 0.911.The expression of hsa_circ₀013958 is closely related to the patient ’s FIGO stage（P = 0.029）and lymph node metastasis（P =0.005）,but not to the patient ’s age,menopause,tumor differentiation,and drug resistance（all P> 0.05）.The results of CCK8 experiment showed that after silencing hsa_circ₀013958in ovarian cancer cells,compared with the blank control group,the proliferation ability of ovarian cancer cells silencing hsa_circ₀013958 was significantly reduced.Transwell experimental results showed that after silencing hsa_circ₀013958 in ovarian cancer cells,compared with the blank control group,the ability of migrating and invasion of ovarian cancer cells that silenced hsa_circ₀013958 was significantly reduced.The results of flow cytometry showed that after silencing hsa_circ₀013958in ovarian cancer cells,compared with the blank control group,the apoptosis rate of ovarian cancer cells silencing hsa_circ₀013958 was significantly increased.Western Blot results showed that after silencing hsa_circ₀013958 in ovarian cancer cells,E-cadherin protein expression increased and Vimentin protein expression decreased compared with the blank control group,indicating that silencing hsa_circ₀013958inhibited epithelial mesenchymal transformation,thus inhibiting the migration and invasion of ovarian cancer cells,which was consistent with Transwell results.After hsa_circ₀013958 was silenced in ovarian cancer cells,compared with the blank control group,the Bax protein expression increased and the Bcl-2 protein expression decreased.It showed that after silencing hsa_circ₀013958,the apoptosis of ovarian cancer cells increased,which was consistent with the results of flow cytometry.Conclusion:1.Hsa_circ₀013958 is highly expressed in ovarian cancer cells and tissues,and its expression is not significantly different in ovarian cancer sensitive and drug-resistant cells and tissues.2.Hsa_circ₀013958 has good diagnostic efficacy for ovarian cancer,3.Hsa_circ₀013958 is closely related to the patient’s FIGO stage and lymph node metastasis,and is not related to the patient’s age,menopause,tumor differentiation,and drug resistance.4.Hsa_circ₀013958 promotes the proliferation,migration and invasion of ovarian cancer cells and inhibits apoptosis.It may affect the biological behavior of ovarian cancer cells through epithelial-mesenchymal transition and apoptosis-related proteins.