The Expression Of Osteosarcoma Amplified-9 And Clinical Significance In Patient With Craniopharyngioma

Objective:Craniopharyngioma is a congenital epidermal tumor that grows along the embryonic craniopharyngial pathway.Although it is a benign tumor,but it is often characterized by invasive growth and calcification,which is closely related to important structures such as cavernous sinus,internal carotid artery,pituitary stalk,hypothalamus,and visual pathway.Postoperative complications and high recurrence rate seriously affect the prognosis of patients.Craniopharyngioma has made some achievements in molecular biology,but its pathogenesis has not been clearly understood.Osteosarcoma amplified-9(OS-9)and matrix metalloproteinase-9(MMP-9)are highly expressed in various human tumor tissues,which are closely related to tumor invasion,proliferation and metastasis.MMP-9 has proved to play an important role in the invasion and recurrence of craniopharyngioma,but the role of OS-9 in craniopharyngioma has not been reported.To investigate the expression of OS-9 and MMP-9 in craniopharyngioma,in addition,the relationship between OS-9and MMP-9 and clinicopathological features as well as relative significance in patient with craniopharyngioma were also explored in present study.Methods:1.The 6 specimens of craniopharyngioma were detected by high-throughput whole exome sequencing.2.According to the inclusion criteria,90 specimens of craniopharyngioma were randomly selected from Neurosurgery Department of the first affiliated Hospital of Zhengzhou University from March 2013 to December 2015,which were treated by microsurgery and confirmed by pathology.And the patients clinical data were collected for analysis.The expression of OS-9 and MMP-9 in 90 cases of craniopharyngioma and 4 cases of normal brain tissue were studied by immunohistochemistry.And Western Blot was used to compare the expression levels of OS-9 protein in craniopharyngioma and normal brain tissue samples.Results:1.Gene test results: There were 12 gene mutations found in 6 patients with craniopharyngioma by whole exome sequencing(IGHG1,OS-9,H-RAS,LOC,SP8,EGFR,CTNNB1,AGAP6,CACNA1 C,DPYD,KDR and BRAF).Among them,os-9,IGHG1,H-RAS had a high incidence of gene mutation in craniopharyngioma,which was 33%.2.The results of immunohistochemistry: OS-9 and MMP-9 were expressed in cytoplasm.The positive expression rate of OS-9 in 90 cases of craniopharyngioma was 88.89%(80 / 90).According to the percentage of positive staining cells,they were divided into(+)14.44%(13 / 90),(++)48.89%(44 / 90),(+++)25.56%(23 /90).In adamantinomatous craniopharyngioma,OS-9 was mainly expressed in the columnar epithelial cells arranged in the outer palisade and the swirl cell cluster in the inner layer,while in papillary craniopharyngioma,it was mainly expressed in the basal layer cells.The expression level of OS-9 was significantly higher in invasive adamantinomatous craniopharyngioma than in non-invasive adamantinomatous craniopharyngioma,and the difference was statistically significant(P<0.05).The expression level of OS-9 was significantly higher in recurrent craniopharyngioma than in non-recurrent craniopharyngioma,and the difference was statistically significant(P<0.05).However,there was no significant difference in the expression level of OS-9 in patients with sex,age,tumor nature and tumor histological type(P>0.05).The expression of OS-9 and MMP-9 in craniopharyngioma was positively correlated(P < 0.05).3.Western Blot results: the expression level of OS-9 protein was significantly higher in craniopharyngioma tissues than in normal brain tissues,and the difference was statistically significant(10.05 ± 1.25% / 20.43 ± 1.36%,P<0.01).Conclusions:1.This study found that OS-9 has a higher gene mutation in craniopharyngioma.2.The increased expression of OS-9 in craniopharyngioma may play an important role in the occurrence and development of craniopharyngioma.3.The high expression of OS-9 in craniopharyngioma may increase tumor invasiveness by inducing the expression of MMP-9.