The Expression And Clinical Significance Of B7-H4, OPN And P53 In Epithelial Ovarian Tumors

Objective:Investigate the expression and clinical significance of the B7-H4, OPN and P53 in epithelial ovarian cancer, borderline ovarian tumor, ovarian benign tumor, normal ovarian tissue and their relationship, as well as the relation to clinical or pathological factors of epithelial ovarian cancer. Investigate the prognostic factors in epithelial ovarian cancer.Methods:The expression of B7-H4, OPN and P53 were detected by immuno-histochemistry for 35 cases of epithelial ovarian cancer,17 cases of borderline ovarian tumor,15 cases of ovarian benign tumor and 6 cases of normal ovarian tissue. Pearson chi-square test, Fisher's exact test and Spearman correlations statistical methods were utilized to analyze the expression of the B7-H4, OPN and P53 in epithelial ovarian cancer and their relationship. Cox regression was used for the survival analysis of the epithelial ovarian cancer.Results:1. B7-H4 staining was located on the tumor cell membrane and cell cytoplasm. The positive rate of B7-H4 in epithelial ovarian cancers was 86%(30/35), which was significantly higher than in borderline ovarian tumors(71%), benign ovarian epithelial tumors(40%)and normal ovarian tissues(0%),which was statistically significant (P<0.05). The expression of B7-H4 in epithelial ovarian cancer correlated with cell differentiation and FIGO stage(P<0.05). And the positive rate of B7-H4 in early stage (stageⅠ+stageⅡ) was high, which was 88.9%.2. OPN staining was located on the tumor cell cytoplasm. The positive rate of OPN in epithelial ovarian cancers was 69%(24/35) which was significantly higher than in benign ovarian epithelial tumors(26%)and normal ovarian tissues(0%) (P< 0.05). The expression of OPN was positively correlated with the level of serum CA125 in epithelial ovarian cancer (rs=0.447, P<0.05).3. P53 staining was located on the tumor cell nucleus. The positive rate of P53 in epithelial ovarian cancer was 77%(27/35), which was higher than in borderline ovarian tumors(59%), benign ovarian epithelial tumors(0%) and normal ovarian tissues (0%) (P< 0.05).The expression of P53 positively correlated with the expression of B7-H4 (rs=0.361, P<0.05). The expression of P53 correlated with FIGO stage (P<0.05).4. Multivariate COX regression analysis showed that the prognosis of epithelial ovarian cancers correlated with FIGO stage. The expression of B7-H4, OPN and P53 were not the independent prognosis factors of epithelial ovarian cancer (P>0.05).5. Diagnostic sensitivity of B7-H4 protein combined with P53 protein was significantly increased from 85.7% to 97.1% and specificity went down from 52.6% to 47.4%, which contributed to the early diagnosis of the ovarian cancer.6. The expression of B7-H4 in borderline ovarian tumors positively correlated with the expression of P53(rs=0.565, P<0.05) and the expression of OPN(rs=0.592, P<0.05).Conclusions:B7-H4, OPN and P53 over express in epithelial ovarian cancer. There was positive correlation in epithelial ovarian cancer between the expression of B7-H4 and P53. And both of them were positively correlated with FIGO stage. The expression of B7-H4 was correlated with cell differentiation. The lower cell differentiation of epithelial ovarian cancer was, the higher B7-H4's expression was. And the positive rate of B7-H4 in early stage of epithelial ovarian cancer was high. The expression of OPN positively correlated with the level of serum CA125, and it will be another biomarker to diagnose, monitor and evaluate early stage ovarian cancer. B7-H4 protein combined with P53 protein in diagnostic sensitivity significantly increased, which contributed to the early diagnosis of ovarian cancer. The prognosis of epithelial ovarian cancer correlated with FIGO stage. The expression of B7-H4, OPN and P53 were not independent prognosis factors of the epithelial ovarian cancers. The study of the expression of B7-H4,OPN and P53 provides a new way in epithelial ovarian cancer as the immune adjuvant therapy.