Research On The Correlation Of SOX2 And HIF-1? With Neoadjuvant Chemotherapy In Locally Advanced Cervical Squamous Cell Carcinoma

Background and objective:Because of the large volume of local cancer,the curative effect of traditional surgery and radiotherapy in locally advanced cervical cancer?LACC?is not ideal.At present,NACT followed by radical surgery serves as one of the first-line treatments of LACC in China,but for patients who are not sensitive to chemotherapy,NACT may delay the beginning of effective treatment.There are still no indicators that can predict or evaluate the efficacy of NACT in LACC.But there are loads of studies suggest that the abnormal expression of SRY-related HMG box2?SOX2?and hypoxia-inducible factor-1??HIF-1??are closely related to the occurrence,development,invasion,metastasis and poor prognosis of many kinds of malignant tumors,including cervical cancer.And some studies have further shown that both of them may contribute to drug resistance.The purpose of this research is to investigate the expression levels of SOX2and HIF-1?in locally advanced cervical squamous cell carcinoma before and after NACT and their clinical significance.Materials and methods:A total of 120 patients with?_B2or?_A2 cervical squamous cell carcinoma who underwent radical hysterectomy after two courses of NACT in our hospital from 2010 to2013 were collected.Collected and recorded the patient's age,menarche age,age at first sex,number of pregnancy,number of birth,tumor volume before and after NACT and FIGO staging,their correlation with NACT efficacy were analyzed.Immunohistochemical sections were made from the paraffin-embedded tissue blocks of cervical biopsy before NACT and surgery after NACT and stained with SOX2.The immunohistochemical sections of HIF-1?were made in the same manner as SOX2.The above included cases were divided into different subgroups based on tumor volume before and after NACT and the World Health Organization's evaluation criteria for solid tumor treatment.The expression of SOX2 and HIF-1?in different subgroups and its clinical significance were analyzed.Result:There were no significant difference in the data of age,menarche age,age at first sex,number of pregnancy,number of birth,tumor volume before NACT,FIGO staging among different groups?P>0.05?.The complete remission group was 27/120?22.5%?,and the partial remission group was 75/120?62.5%?,that was,the effective rate of NACT was 102/120?85%?;the stable disease group was 12/120?10%?,and progressive disease group was 6/120?5%?,that was,the ineffective rate was 18/120?15%?.Both SOX2 and HIF-1?positively expressed in the cervical squamous cell carcinoma,while SOX2 and HIF-1?were almost negative in complete remission cases after NACT.There was no significant difference in the expression level of SOX2 in all groups before NACT?P>0.05?,while that of post NACT in effective group showed a obvious downward trend?P<0.01?.Except no significant difference of expression level of SOX2 after NACT and expression change of SOX2 between SD group and PD group,there were statistical differences of that between the other groups?P<0.05?,suggesting that the change in the expression level of SOX2 had a good correlation with the efficacy of NACT.The expression level of HIF-1?before NACT only had statistical difference between SD group and PD group?P<0.01?.Except CR cases,HIF-1?showed an upward trend after NACT?P<0.05?.There was difference in HIF-1?expression level after NACT and expression change of HIF-1?between the effective group and the ineffective group?P<0.01?,but further comparison of the four subgroups revealed that the statistical difference only existed when comparing CR group with the other three groups?P<0.01?,respectively,suggesting that NACT would have an influence on the expression level of HIF-1?,and different subgroups would get different effect.Conclusion:1.SOX2 might not be a predictor of the efficacy of NACT,but the decrease of SOX2 expression level after NACT is positively correlated with the sensitivity of it,which the possible reason is that chemotherapy inhibits the expression of SOX2 in cancer stem cells.Monitoring changes in SOX2 levels can help to evaluate the efficacy of NACT.2.HIF-1?might not be a predictor of the efficacy of NACT,but the expression of HIF-1?decreased significantly in complete remission cases after NACT,but increased significantly in patients with partial remission,stable disease,and disease progression,which might be related to the changes after NACT in microenvironment of cancer.