Expression Of B7-H4 In Prostate Cancer And Its Effect On Stemness Characteristics

Objective:To investigate the expression of B7-H4 in PCa and its effect on the stemness characteristics of prostate cancer,and thus to be used as a molecular target for the development of treatments for PCa.Methods:Immunohistochemistry was used to observe the expression of B7-H4 in 14 cases of benign prostatic hyperplasia and 148 cases of prostate cancer,and to detect the expression of cell cycle related genes and genes related to PI3K/Akt signaling pathway activation in prostate cancer tissues.Analyze the relationship between B7-H4 and clinicopathological features of prostate cancer,Kaplan-meier survival curve was used to analyze the relationship between B7-H4 expression in prostate cancer tissues and the prognosis of patients.Immunofluorescence and Western blotting were used to detect markers related to tumor stemness characteristics in B7-H4 expression in prostate cancer tissues,PC3,DU145 and LNCaP PCa cell lines.Silencing B7-H4 gene expression using esiRNA transfection technology,using Western blot to verify the transfection effect,and further using invasion and migration experiments to detect the effect of B7-H4 expression down-regulation on the invasion and migration ability of PC3 and DU 145 cell lines.Results:1.The positive expression of B7-H4 in prostate cancer tissue is significantly higher than that in benign prostatic hyperplasia(P<0.001).2.The overall survival rate of the B7-H4 positive group was significantly lower than that of the negative group(P=0.011).3.B7-H4 was closely correlated with tumor stem cell markers Sox2(P=0.026),Sox9(P=0.045)and CD44(P=0.017),and B7-H4 was co-expressed with Sox2 and Sox9 in PCa cells.4.In PC3 and DU145 cell lines,the expression levels of Sox2,Sox9 and CD44 in the silenced B7-H4 group were significantly lower than those in the control group,and the number of invasive and migratory cells in the silenced B7-H4 group was significantly lower than those in the control group(P<0.001).5.Statistical analysis showed that the expression of B7-H4 was positively correlated with the expression of PCa cell cycle related factors such as CDK4(P=0.033)and cyclinD1(P=0.001)and the expression of PI3K/Akt signaling pathway activation related factors such as pPI3K(p85)(P=0.003)and pAkt-ser473(P<0.001).Conclusion:1.High expression of B7-H4 may be a effective target for the prognostic evaluation of PCa patients.2.B7-H4 may be related to prostate cancer stemness characteristic markers.3.B7-H4 may play an important role in the invasion and migration of PCa.