Expression Pattern And Biological Significance Of Thrombospondin-4in Prostate Cancer

ObjectiveTo investigate the role of THBS4in prostate cancer invasion and metastasis, and to further clarify its expression mechanism in xenotransplantation animal modelsMethodsWe used cDNA microarray to compare gene expression profiles of cancerous area and adjacent non-cancerous core tissues from8PCa patients unfixed prostatectomy specimens. For the purpose of functional annotation of differentially expressed genes, we used literature retrieval, network software and bioinformatics online tools. To understand the biological function of the differentially expressed genes, participation in the composition of ingredients, involved in the regulation of signal transduction pathways and protein-protein interaction networks.We clarified the carcerous and their pericarcinous tissues biological differences.We selected the THBS4gene as the research object. In order to verify the results of microarry, we used RT-PCR and immunohistochemical detection method. THBS4selected as the research object. In order to verify the results of gene chip, we use10cases of fresh prostate cancer specimen and non-cancerous prostate glands for RT-PCR and immunohistochemistry. To investigate the mechanism(s) responsible for THBS4expression in prostate cancer, we have studied the role of THBS4in mediating progression of prostate cancer, expression characteristics and possible mechanism of action. We tested60cases of prostate cancer paraffin for the presence of THBS4protein.This outcome was in combination with standard clinical information provides reliable prognostic prediction of prostate cancer statistically. Based on that microsurgical technique, we establishing human prostate cancer and benign prostate hyperplasia xenograft model in mice.Further, we performed Immunohistochemistry and H&E staining to detect THBS4expression in the two models.ResultsGene expression studies have made it clear that there is considerable difference among tumors and the adjacent tissues. THBS4genes showed consistent high expression in prostate cancer. These were confirmed by RT-PCR and immunohistochemistry assay. THBS4selectively expressed in reactive stromal fibroblasts or eptithelial cells.Expression of THBS4is associated with Gleason Score, pathology type and TNM stage. Expression of THBS4is associated with Gleason Score, pathology type and TNM stage.COX regression analysis showed that high THBS4expression was associated with significantly decreased survival in patients with prostate cancer. The patient-derived human prostate cancer and benign prostate hyperplasia xenograft model in NOD/SCID mice is successfully established. These models have been shown to facilitate the investigation of etiology mechanism of PCa. In mouse model, the expression of THBS4was similar with original tissue. THBS4is highly expressed in epithelial cells of prostate cancer of mice model, and the expression close to the edge of kidney is even higher than tumor core stroma.ConclusionTHBS4could become as different malignant degree or different stages of mesenchymal markers of prostate cancer. The expression level of THBS4combinated with Gleason score and pathological types can offer uesful predictive value.