Expression Of FOXC2 In Malignant Glioma And Its Clinical Significance

Background and purposeMalignant glioma,also known as glioma or keratinoma,is the most common type of primary malignant brain tumor,accounting for about 80%.The incidence of malignant glioma is the first of all kinds of malignant tumors in the brain.It belongs to neuroepithelial malignant tumors,accounting for 40%-50%of all tumors in the brain.Malignant glioma patients has the clinical characteristics of high incidence,low cure rate and high recurrence rate.The incidence of malignant gliomas increases with age.The growth of malignant gliomas is often invasive,and tumor cells often infiltrate into normal brain tissue.The treatment is mainly a combination of surgery and radiotherapy and chemotherapy,the prognosis of malignant glioma patients is poor,and the annual survival rate is only about 30%.Previous studies have shown that abnormal proliferation of tumor cells in malignant gliomas and angiogenesis in cancer cell clusters are the most critical factors for chemoradiation resistance and disease recurrence.FOXC2,the forkhead box protein C2 or mesenchymal fork protein 1,as a transcription factor that regulates the growth and development of the vasculature,and regulates the epithelial-mesenchymal transition process of tumor cells and has been found in the mammary gland.It is highly expressed in various tumor tissues such as breast cancer and gastric cancer and is associated with metastasis.Therefore,FOXC2 may be used as a potential tumor treatment target to provide new ideas or ways for the diagnosis and treatment of various malignant tumors.Therefore,this study selected 100 patients with malignant glioma undergoing surgery to detect the expression of FOXC2 in malignant glioma samples,and to analyze its correlation with clinical pathological data,prognosis and recurrence sites,in order to understand the expression of FOXC2 in malignant gliomas and its effects on tumor prognosis and recurrence sites.methodOne hundred cases of malignant gliomas patients receiving hospitalization in neurology in the First Affiliated Hospital of Zhengzhou University from October2015 to October 2017 were included.The patients were included in the following criteria.The intraoperative pathology was confirmed as malignant glioma;no radiotherapy or chemotherapy was received before surgery;the initial diagnosis was malignant glioma;the medical records were complete.The following patients were excluded.Patients were combined with other systemic tumors with brain metastases,hematological tumors,endocrine system diseases,and other investigators.One hundred cases(control group)with brain tissue removed due to non-tumor causes such as trauma were selected.There was no significant difference in the general data between the malignant glioma group and the control group(p>0.05).The expression of FOXC2 in malignant glioma and brain tissue samples was detected by immunohistochemical staining,and the positive expression of FOXC2 in tissues was observed.Patients with malignant gliomas were followed up for the first time on admission,and the follow-up deadline date was October 30,2018.Progression free survival time(PFS)was defined as the time from the start of surgery to the first time of recurrence or metastasis or the last follow-up.Overall survival(OS)was defined as the time from the start of surgery to the first discovery of all-cause death or the last follow-up.To observe the positive expression of FOXC2 in malignant glioma tissues and normal brain tissues.The correlation between expression of FOXC2 in malignant gliomas and clinical pathological factors(age,gender,postoperative radiotherapy,resection range,comprehensive treatment,radiotherapy dose,surgery to radiotherapy time,tumor differentiation,tumor volume,tumor range,ventricular system invasion,number of tumors,preoperative seizures,Karnofsky PS score)were analyzed by Fisher's exact probability method and?~?test.Kaplan-Meier analysis,rank-rank analysis and Cox regression model were used to analyze the relationship between FOXC2 expression and patient prognosis(PFS,OS).The correlation between recurrence site and FOXC2 expression was analyzed.result1.The positive rate of FOXC2 expression in the malignant glioma group was50.0%,which was higher than that in normal brain tissue(6.0%),the difference was statistically significant(p<0.05).2.Patients with positive FOXC2 expression and patients with negative FOXC2expression had statistically significant differences in tumor differentiation,preoperative seizures,Karnofsky PS score,tumor volume,tumor extent,and ventricular system invasion,the difference was statistically significant(p<0.05).The degree of tumor differentiation,preoperative seizure rate,and ventricular system involvement rate were higher in FOXC2 positive patients than those in FOXC2negative patients.Tumor volume and tumor range in FOXC2 positive patients were larger than those in FOXC2 negative patients.The Karnofsky PS score in FOXC2positive patients was lower than that in FOXC2 negative patients.3.The follow-up period was 12-36 months,and the average follow-up time was25.1 months.A total of 5 patients were lost to follow-up,the effective follow-up rate was 95.0%.The Kaplan-Meier method and the rank-rank test showed that there was a statistically significant difference in the PFS rate and OS rate between the FOXC2positive group and the FOXC2 negative group(p=0.07,0.01).The Cox proportional hazard model showed that the FOXC2 expression(95CI:1.106-5.217),tumor volume(95CI:1.086-4.159),postoperative radiotherapy(95CI:1.028-2.947),tumor differentiation(95CI:1.651-6.847),and Karnofsky PS score(95CI:1.109-4.671)were independent prognostic factors for PFS in patients with malignant glioma(p<0.05).The expression of FOXC2(95CI:1.689-6.314),age(95CI:1.101-3.574),degree of tumor differentiation(95CI:1.103-5.361),and Karnofsky PS score(95CI:1.359-4.958)were independent prognostic factors for OS of patients with malignant glioma(p<0.05).Malignant gliomas patients with positive FOXC2 expression had lower PFS and OS rates.4.The recurrence rate of malignant glioma patients was 61.9%,and the recurrence rate of distant sites was 25.4%.Multivariate analysis showed that ventricular system invasion(95CI:1.147-7.214)and FOXC2 expression(95CI:1.084-5.661)were independent factors influencing the recurrence site of malignant glioma patients(p<0.05).Patients with malignant gliomas with ventricular system involvement and positive FOXC2 expression are more likely to have recurrence in distant sites.conclusion1.The positive rate of FOXC2 expression in malignant glioma tissues is higher than that in normal brain tissues.2.The expression of FOXC2 was correlated with the clinicopathological data of patients.The degree of tumor differentiation,preoperative seizure rate,and ventricular system involvement rate were higher in FOXC2 positive patients than those in FOXC2 negative patients.Tumor volume and tumor range were larger in FOXC2 positive patients than those in FOXC2 negative patients.The Karnofsky PS scores was lower in FOXC2 positive patients than that in FOXC2 negative patients.3.The expression of FOXC2 was correlated with PFS and OS in patients with malignant glioma during follow-up.Patients with positive FOXC2 expression had shorter PFS and OS than patients with negative FOXC2 expression.Malignant gliomas patients with positive FOXC2 expression,tumor volume>60.0 cm~3,no postoperative radiotherapy,grade III or IV tumor differentiation,and low Karnofsky PS score were more likely to have recurrence and metastasis after surgery.Patients with malignant gliomas with positive FOXC2 expression,elderly patients,grade III or IV tumor differentiation,and low Karnofsky PS scores had lower survival rates.4.Malignant glioma mainly recurrence in situ.The recurrence site was associated with the invasion of the ventricular system and the expression of FOXC2.Patients with malignant gliomas with ventricular system involvement and positive FOXC2 expression are more likely to have recurrence in distant sites.