Role of Human Epididymis Protein 4 (HE4) in Determining Survival of Patients With Endometrial Cancer: A Meta-Analysis

Background: Human epididymis protein 4 (HE4) is a novel cancer biomarker. This study evaluates the prognostic role of HE4 in determining the survival of endometrial cancer patients. Methods: Literature search was conducted in electronic databases (Embase, Ovid, PubMed, Scopus, and Web of Science). Studies were selected if they reported the relationship between HE4 and the survival of endometrial cancer patients. Random-effects meta-analyses were performed to achieve estimates of baseline serum HE4 levels, the 5-year survival with high and low serum HE4 levels/expression, and the hazard ratios (HRs) of the survival between patients with high and low serum HE4 levels. Results: 9 studies (1404 patients; age 63.1 years [95% confidence interval (CI): 61.2, 64.9]; follow-up 35.9 months [95% CI: 32.2, 39.6]) were included. In these patients, serum HE4 levels were 83.36 picomole/liter (pM) [95% CI: 70.15, 96.56] overall but these were higher in patients with recurrence (108.13 pM [95% CI: 63.09, 153.18] and lower in patients with no recurrence (67.88 pM [95% CI: 65.09, 70.67]). The 5-year overall survival rate was higher in patients with low HE4 levels/expression (86% [95% CI: 79, 92] but lower in patients with high HE4 levels/expression (63% [95% CI: 58, 68]. A pooled HR of survival between patients with high and low serum HE4 levels of 2.25 [95% CI: 1.56, 2.94] indicated shorter survival in patients with high serum HE4 levels. Conclusion: High HE4 concentrations in patients with endometrial cancer are found to be associated with shorter survival.