| Objective:Cerebral astrocytoma originates from neuroepithelium and is the most common primary intracranial tumor,accounting for 45.2%-71.0 of intracranial neuroepithelial tumor.Astrocytoma is characterized by invasive growth,frequent recurrence and poor prognosis.The 5-year survival rate of patients with astrocytoma is about 25%.Especially,the 5-year survival rate of patients with Glioblastoma is less than 3%.Nowadays,the treatment for astrocytoma mainly comprises surgical resection,radiotherapy and chemotherapy.The genetic therapy and molecular targeted therapy for astrocytoma have become prevalent today.Therefore,to explore the mechanism of development and progression of astrocytoma and to identify new therapeutic target are extremely significant to treatment for astrocytoma in future.Homeobox gene family(HOX family for short)which is associated closely with human cancers.HOX family includes HOXA,HOXB,HOXC and HOXD subtribes.The four subtribes are located on chromosomes 7,17,12 and 2,respectively.HOXB5 is a member of HOXB subtribe,located on chromosome 17(17p21.32).HOXB5 gene could encode a DNA-binding transcription factor,which involves in gene expression,cell differentiation and the occurrence of body morphology.In addition,HOXB5 was found to play an important role in the differentiation of hematopoietic stem cells and epithelial cells.Moreover,HOXB5 expression `was detected in several organs such as lung,kidney and breast,and correlated to the development of lung and neuronal crest.HOXB5 was found to affect the growth of a variety of cancers.So far no research involving HOXB5 and astrocytoma has been published.In the present study,immunohistochemtry and western tests were using to detect the expression of HOXB5 in astrocytoma.Subsequently,postoperative the follow-up of patients with Glioblastoma was performed to investigate the role of HOXB5 in development and progress of astrocytoma.The new theory basis or idea may be obtained for genetic therapy of astrocytoma.Methods: 1.Immunohistochemistry staining was used to test HOXB5 expression in tumor samples from 20 cases with diffuse astrocytoma(WHO Grade ?),20 cases with anaplastic astrocytoma(WHO Grade ?),tumor samples from 20 patients with Glioblastoma and non-neoplasm brain samples from 20 severe traumatic brain injury cases.Furthermore,the relationship between HOXB5 and clinical pathological characteristics and association of HOXB5 with Ki-67 were analyzed.2.The expression of HOXB5 protein in 60 cases with astrocytoma and 20 cases with severe traumatic brain injury described above was detected using Western Blot tests.The follow-ups of patients with Glioblastoma were performed after discharge to obtain the survival period.The correlation between HOXB5 and survival of Glioblastoma patients was analyzed.3.SPSS19.0 software was applied.The experimental data was analyzed by Chi-square test,t test,ANOVA test,spearman correlation analysis.Results: 1 Expression of HOXB5 in astrocytoma 1.1 Immunohistochemistry staining Among 60 astrocytoma patients,HOXB5 was positive expression in 35 cases,the positive expression rate was 58.3%(35/60).Only one out of 20 control cases was positive for HOXB5,the positive expression rate was 5%(1/20).The positive expression rate of HOXB5 in astrocytoma was significantly higher than that in normal brain tissue(P<0.05).The positive expression rates of HOXB5 protein in diffuse astrocytoma,anaplastic astrocytoma and glioblastoma were 15%(3/20),65%(13/20)and 95%(19/20),respectively.The positive expression rate of HOXB5 increased significantly with the level of astrocytoma(P<0.05),among which,the positive expression rate of HOXB5 in glioblastoma was significantly higher than that in anaplastic astrocytoma and diffuse astrocytoma(P<0.05),and the positive expression rate of HOXB5 in anaplastic astrocytoma was significantly higher than that in diffuse astrocytoma(P<0.05).However,the HOXB5 positive expression rate in diffuse astrocytoma was not statistically different from that in normal brain tissue(P>0.05).1.2.Western Blot Western Blot results indicated that HOXB5 protein expression level increased along with the grade of astrocytoma(P<0.05).In additionally,HOXB5 expression level in glioblastoma was significantly higher than that in anaplastic astrocytoma and diffuse astrocytoma(P <0.05).HOXB5 expression in anaplastic astrocytoma were significantly higher than that in diffuse astrocytoma(P<0.05).However,the expression level of HOXB5 in diffuse astrocytoma was not statistically different from that in normal brain tissue(P>0.05).2 The expression of Ki-67 in astrocytoma Immunohistochemical staining results showed that protein positive expression rate of K-67 is 10%,75% and 100% in ?-? astrocytoma respectively.With astrocytoma grade gradually increase,positive expression rate of Ki-67 raised(P<0.001).3 The relationship between expression of HOXB5 protein and clinic pathological features of patients The positive expression rate of HOXB5 was independent of gender,age,tumor size and tumor location of patients with astrocytoma(P>0.05).4 Correlation analyses between HOXB5 expression and ki-67 expression Spearman correlation analysis showed HOXB5 protein expression was positively correlated with the expression of Ki-67 in astrocytoma(P <0.001).5 Correlation analyses between HOXB5 expression level and survival time of glioblastoma patients In this study,20 patients with glioblastoma were followed up to obtain their survival time.According to HOXB5 expression level measured in 20 cases and compare with the average expression level,20 patients with glioblastoma were divided into high-HOXB5 group and low-HOXB5 group.After Log-Rank test,we found that the average survival time of patients in low-HOXB5 group was significantly longer than that of patients in high-HOXB5 group(P=0.041).The result indicated that the expression level of HOXB5 in glioblastoma correlated with patients' survival time.Conclusion: 1.HOXB5 played an important role in the occurrence and progression of anaplastic astrocytoma and glioblastoma.2.The expression of HOXB5 in astrocytoma is positively correlated with ki-67,which suggested that HOXB5 may be related to proliferation activity of astrocytoma.3.There was a significant negative correlation between HOXB5 expression level and the average survival time of GBM patients.It was suggested that HOXB5 can be regarded as an important indicator to evaluate the prognosis of glioblastoma patients. |
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