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

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.