Prognostic values of human epididymis protein 4 expression in patients with endometrial cancer: A systematic review and meta-analysis.

Abstract

There is no consensus on the correlation between human epididymis protein 4 (HE4) and prognosis of endometrial cancer (EC). Therefore, we performed a meta-analysis to assess the relationship between HE4 and prognosis of EC. In this systematic review and meta-analysis, the databases were searched. Correlation of serum or tissue HE4 with clinicopathological characteristics was determined by odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI), respectively. The hazard ratio (HR) with 95% CI was calculated to evaluate the correlation between HE4 and survival outcome. A total of 38 published studies were eligible. We found that high levels of serum HE4 were associated with FIGO III-IV stage (SMD=1.58, 95%CI: 1.18-1.98, p < 0.001), grade 3 (SMD=0.66, 95%CI: 0.39-0.93, p=0.001), ≥50% myometrial invasion (SMD=0.78, 95%CI: 0.58-0.99, p < 0.001), lymphovascular space invasion (SMD=0.82, 95%CI: 0.54-1.11, p=0.001), lymph node metastasis (SMD=1.27, 95%CI: 0.84-1.69, p < 0.001), cervical involvement (SMD=0.71, 95%CI: 0.43-0.98, p=0.003), parametrial involvement (SMD=1.03, 95%CI: 0.71-1.35, p < 0.001) and peritoneal cytology (SMD=0.49, 95%CI: 0.22-0.75, p < 0.001). High expression of tissue HE4 was only significantly associated with lymph node metastasis (OR=6.19, 95%CI: 2.07-18.50, p=0.001). High levels of serum HE4 were significantly associated with poor overall survival (univariate: HR=3.77, 95%CI: 1.94-7.32, p < 0.001; multivariate: HR=2.15, 95%CI: 1.65-2.80, p < 0.001) and disease-free survival (univariate: HR=2.89, 95%CI: 2.14-3.88, p < 0.001; multivariate: HR=2.31, 95%CI:1.20-2.67, p < 0.001) in EC. Compared with cancer antigen 125, serum HE4 may be a better prognostic indicator for EC. High HE4 expression is associated with poor prognosis of EC and may be a potential prognostic biomarker for EC.