The Nuclear Expression Of B7-h4in Renal Cell Carcinoma And The Effect Of B7-h4Nuclear Localization Sequence On HEK293Cells Growth In SCID Mice

Objective:To investigate the expression of B7-H4in the nucleus of renal cell carcinoma and the relationship between the B7-H4expression level and the clinicopathological characteristics; Construction of SCID mice transplantation tumor model using the wild type of B7-H4cells (B7-H4WT) and the mutant cells of nuclear localization of B7-H4cells (B7-H4H250Q MT), then to study the effect of B7-H4nuclear localization sequence on HEK293cells growth.Methods:Collected82cases of surgical resection of renal cell carcinoma specimens as the experimental group, use the method of immunohistochemical to detect the expression of protein levels, and collected clinical data to analysis of the relationship between their localization of expressing; We implanted cells in severe combined immunodeficiency mice to establish xenograft model:24severe combined immunodeficiency mice were divided into three groups and in each group, eight mice were injected with B7-H4WT/293, Mock/293or B7-H4H250Q MT/293cells, The number of subcutaneous injection at a dose of2X107cells. In the groups that mice were implanted with two different cells on contralateral sides. The mice were sacrificed and tumors were obtained8weeks after the injection, measurement results of the transplanted tumor volume and quality, and the expression of B7-H4in tumor sample were detected by immunohistochemistry.Result:1.The B7-H4was significantly expression in RCC tissues of membranous, cytoplasmic and nuclear; the nuclear and membranous expression of B7-H4were significantly associated with tumor classification,2002Tumor, Node, Metastasis(TNM) stage grouping and nuclear grade(P<0.05), and there was no statistically significant correlation with gender, age, symptoms at presentation, tumor size, distant metastases at nephrectomy (P>0.05).2. It was observed that tumor size and weight was significantly enhanced in the group injected with B7-H4WT/293cells compared with the group injected with Mock/293cells and the group injected with B7-H4H250Q MT/293cells(P<0.05), but there was no significant difference between B7-H4H250Q MT/293group and Mock/293group(P>0.05).3. Immunohistochemical staining showed that B7-H4was highly expressed in nucleus derived from B7-H4WT/293, but rarely expressed in nucleus from Mock/293cells and B7-H4H250Q MT/293cells.Conclusion:The result suggesting that the nuclear localization of B7-H4might be correlated with clinical outcome in RCC, nuclear localization of B7-H4might be significantly promoted the growth of HEK293cells in SCID mice, it suggest that the B7-H4expression may become a new gene therapy strategy for advanced renal cell carcinoma. It may help to study the development of renal cell carcinoma to investigate the expression and nuclear localizations of B7-H4,so it might be a promising strategy for the treatment.