Differential Expression Of Gab2 And BMI1 In Primary Osteosarcoma And Matched Lung Metastasis And Its Clinical Significance

ObjectionTo study the expression levels of Gab2-associated binder family proteins and B cell-specific moloney murine leukemia virus integration site1 genes in osteosarcoma patients and their corresponding lung metastasis tissues.The relationship between the characteristics and prognosis,and the correlation between the expression of Gab2 and BMI 1 genes and the biological behaviors of osteosarcoma,development and metastasis,thus providing a theoretical basis for the prevention and treatment of osteosarcoma.MethodsThe paraffin-embedded specimens of the primary tumors that emerged from the treatment of osteosarcoma patients from February 2010 to June 2015 in our hospital and identified as lung metastases were selected as the primary group,and the lung metastases corresponding to lung puncture or surgical resection were performed.Paraffin specimens were used as metastasis group,including 14 males and 10 females,aged(16.7±4.3)years old.In addition,32 patients with osteosarcoma who had no pulmonary metastasis during the treatment and follow-up were selected in our hospital.The primary lesions were used as the control group,including 15 males and17 females,aged(18.9±7.6)years old.The clinical stage of osteosarcoma primary tumor tissues was determined by Enneking staging method.24 cases in the primary group were stage III,18 cases in stage I,9 cases in stage IIA,and 5 cases in stage IIB.Immunohistochemistry(streptavidin.perosidase,SP)was used to detect the protein encoded by Gab2 and BMI 1 in the primary,metastatic and control groups,and the expression level of Gab2 gene was analyzed with age,sex,tumor size and clinical status.Relationship between prognosis and other aspects.Statistical analysis was performed using SPSS21.0 statistical software.The?~2 test or Fisher's exact probability method was used between the two groups.The correlation analysis was performed by Spearman correlation analysis and the survival analysis was performed by Kaplan.The Meier method was statistically significant at P<0.05.Results1.Expression of Gab2 gene,BMI 1 gene and Ki-67 in primary tumor and lung metastasis of osteosarcoma:Gab2 protein is mainly expressed in the cell membrane and cytoplasm of tumor cells,and BMI 1 protein is mainly located in tumor cells.The cytoplasm,Ki-67 protein is mainly located in the nucleus of tumor cells;the positive rate of expression of Gab2 gene primary group,metastasis group and control group((positive cases+strong positive cases)/The total number of cases)were 37.5%,75%,and 12.5%.The positive rates of BMI 1 gene expression in the primary,metastasis,and control groups were 37.5%,33.3%,and 9.4%,respectively.The Ki-67protein was in the primary.The positive rates of expression in the group,metastasis group and control group were 45.8%,79.2%,and 18.6%,respectively.2.Differences in expression of Gab2 gene,BMI 1 gene and Ki-67 in osteosarcoma primary tumor and lung metastases:in the Gab2 gene,the positive rate was higher in the metastatic group than in the primary group,and both were higher than In the control group,the primary group and the metastatic group(?~2=8.166,P=0.043),the primary group and the control group(?~2=9.087,P=0.028)were statistically significant,and the Gab2 gene expression results were compared with osteosarcoma.In the tumor diameter relationship,the difference between the Gab2 high expression group and the low expression group of osteosarcoma was statistically significant(?~2=9.631,8.680,P=0.006,0.008);the primary rate in the BMI 1 gene was positive.The difference between the primary group and the control group was statistically significant(?~2=9.233,P=0.020),but there was no significant difference between the primary group and the metastatic group(?~2=0.410,P=0.954);The results of Ki-67protein positive rate were higher in the metastatic group than in the primary group,and both were higher than the control group,including the primary group and the metastatic group(?~2=8.514,P=0.037),the primary group and the control group(?~2=8.754,P=0.033)The difference was statistically significant.3.Correlation analysis of Gab2 gene,BMI 1 gene and Ki-67 expression in osteosarcoma primary tumor and lung metastasis:Gab2 gene was positively correlated with Ki-67 protein(r=0.752,P<0.01);In the correlation analysis of BMI 1gene,the two groups of genes with high expression of the primary and metastatic groups were selected,and the results showed that the two genes were negatively correlated(r=-0.655,P<0.01),which may be related to Gab2 gene is associated with inhibition of oncogene expression;in multivariate analysis,Gab2 is between the positive and negative expression groups,and the difference in the maximum diameter of osteosarcoma>5 cm,3-year survival rate and 5-year survival rate is statistically significant.Significance(P<0.01),but not significantly related to patient age and gender.In the survival analysis,Kaplan-Meier method was used to analyze the survival time of follow-up patients.The overall survival and median progression-free survival of Gab2-positive patients were lower than those of Gab2-negative group.Conclusion:1.High expression of the Gab2 gene promotes the growth of osteosarcoma primary tumors.2.Osteosarcoma cell proliferation may be an essential condition for lung metastasis of osteosarcoma.3.High expression of Gab2 gene reduces expression of BMI 1 gene.4.BMI 1 gene has certain clinical significance in the process of osteosarcoma undergoing lung metastasis.