The Expression Of Cyclin D1、CDK4、p16 In Paired Initial And Recurrent Glioma

Background and Objective Gliomas occurs in the neuroectoderm which arise from glial cells derived from the neuroectoderm.In recent years,the incidence of primary malignant brain tumors has increased by 1-2% year by year,and is more common in the elderly.Glioma is a common neurological malignancy in clinic.Even through active treatment such as surgical treatment,combined with radiotherapy and chemotherapy,the median survival time of glioma patients is usually only 15-19 months.The one-year and five-year survival rates of adult patients with high-grade glioma are about 30% and13% respectively.About 18-60 thousand young and middle-aged people die from glioma every year in the world,which caused great mental pain and economic burden to society and families.Why is the prognosis of glioma so poor? In addition to the high degree of malignancy of glioma,easy recurrence is also the main reason.Studies have shown that even giving active treatment,70% of high-grade glioma patients also relapse within 6 months after surgery.Generally,about 90 %of glioma recurrence sites occur within 2 cm of the primary site,and the local recurrence is the main way.After recurrence,The biological behavior of glioma has great changed,such as from low-grade to high-grade development,increased malignancy and invasiveness,reduced sensitivity to treatment,and worse prognosis.This greatly shortens the survival period,reduces the quality of life,threatens the life and healthof glioma patients.Therefore,delaying and preventing the recurrence of malignant glioma is a major problem facing the whole world,which is also a hot topic in recent years.In our study,we compared the expression levels of Cyclin D1,CDK4 and P16 proteins in primary and recurrent glioma tissues.We explored the relationship between the three index and the biological behavior of glioma with increased malignancy and poor prognosis after recurrence,and find provide evidence for finding new targets for clinical treatment.Methods We collect glioma patients treated in People’s Hospital of Zhengzhou University from June 2009 to September 2017 who suffered two times operation were enrolled in the group.And both operations were performed by neurosurgery department of our hospital.A total of 75 patients met the requirements of enrollment.Postoperative pathology was diagnosed by pathologists in our hospital.We collect the whole clinical data and surgical excision specimens after initial and recurrence.Immunohistochemistry(IHC)was used to detect the expression of Cyclin D1,CDK4 and P16 proteins in glioma tissues.This study uses SPSS22.0 statistical software(SPSS company)for data analysis,and P<0.05 means that the difference was statistically significantResults1.The expression of Cyclin D1 protein was localized in the nucleus of tumor cells.The positive expression rates of Cyclin D1 protein in primary and recurrent gliomas were 38.7% and 61.3%,respectively.That means the expression level of Cyclin D1 protein increased after recurrence(P < 0.001).In primary gliomas,the positive rates of Cyclin D1 protein expression in WHO I-II and WHO III-IV grade gliomas were 22.5% and 57.1%,respectively.While in recurrent gliomas,the positive rates of Cyclin D1 protein expression in WHO I-II and WHO III-IV grade gliomas were 38.1% and 70.4%,respectively.This means that whether primary or recurrent gliomas the positive rates of Cyclin D1 protein expression in high-grade gliomas were higher than those in low-grade gliomas.The difference was statistically significant(P<0.05).The expression of Cyclin D1 protein was not correlated with gender,age and histopathological type of glioma,whether primary orrecurrent(P > 0.05).2.The expression of CDK4 protein was localized in the nucleus and cytoplasm of tumor cells.The positive rate of CDK4 protein expression in primary glioma was64%,and in recurrent glioma was 80%.Therefore,the expression level of CDK4 protein increased after glioma recurrence.The difference was statistically significant(P=0.043).The expression of CDK4 protein was not correlated with gender,age,WHO grade and histopathological type of glioma(P > 0.05).3.The expression of P16 protein is localized in the nucleus and cytoplasm of tumor cells.The positive rate of P16 protein expression was 78.7% in primary glioma and 62.7% in recurrent glioma.Therefore,the positive rate of P16 protein expression decreased after glioma recurrence,and the difference was statistically significant(P=0.023).The expression of P16 protein was not correlated with gender,age,WHO grade and histopathological type of glioma(P > 0.05).Conclusion In this study,we compared the expression levels of Cyclin D1,CDK4 and P16 protein in primary and recurrent gliomas,and we draw the following conclusions:1.The expression level of Cyclin D1 protein increased with pathological grade.Compared with the primary glioma,the expression of Cyclin D1 and CDK4 protein in recurrent glioma tissues increased.This indicates that the factors promoting cell proliferation in glioma tissue increase after glioma recurrence.Overexpression of Cyclin D1 and CDK4 proteins suggests that glioma cells with recurrence are more proliferative,malignant and invasive.2.The expression of P16 protein decreased after the recurrence of glioma.These results suggest that the factors that inhibit the proliferation of glioma cells are reduced and the proliferation of glioma cells is uncontrolled after the recurrence of glioma.The loss of P16 protein expression was more serious after recurrence,which suggesting that the malignancy and invasiveness of glioma were higher after recurrence.3.After recurrence,the expression of Cyclin D1,CDK4 and P16 protein becomes more disordered,the expression of proto-oncogene which promotes glioma cell proliferation increases,while the expression of anti-oncogene decreases,.Thissuggest that recurrence glioma has a higher degree of malignancy,stronger invasiveness and worse prognosis.They are also expected to be important indicators for evaluating the malignancy and prognosis of glioma,and may also be effective targets for the treatment of glioma.