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

Abstract

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.

The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies

“…Subsequently, a further 34 articles were excluded for the following reasons: 13 presented insufficient data, 6 did not conduct meta-analysis, 4 explored outcomes that we were not interested in, 4 published not in English, the full text of 3 articles were not available, 2 published duplicated reports, 1 explored exposure that we were not interested in, and 1 conducted less than three original studies. Ultimately, 20 studies ( 7 , 8 , 15 , 19 – 22 , 42 – 54 ) were eligible to be included in the main analysis.…”

“…Table 2 showed the nine meta-analyses that involved 81 original studies in four articles for prognosis ( 8 , 44 , 51 , 54 ). These 4 articles were published between 2017 and 2020.…”

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

“…Dai et al conducted a meta‐analysis of 29 studies on HE4 expression and tumor survival outcome and found that high HE4 expression was associated with poorer OS (HR = 2.15, 95% CI: 1.77–2.62, p < 0.001), and this association was not affected by race or tumor type (EC, ovarian cancer, lung cancer) 4 . He et al performed a meta‐analysis of nine studies on HE4 expression and survival outcomes of EC and found that 5‐year survival was higher in patients with low HE4 concentrations, the pooled HRs analysis showed that high HE4 levels were associated with shorter survival in patients with EC 5 . In our study, we found that high serum HE4 levels were associated with poorer OS and DFS, and in a subgroup analysis, only multivariate analysis model results showed no correlation between high serum HE4 levels and poor OS in non‐occident.…”

“…Recently, more and more studies have reported the evolving role of HE4 in monitoring EC progression and prognosis, but there is heterogeneity in study results and a meta‐analysis is needed. Meta‐analyses regarding HE4 and prognostic value by Dai et al and He et al both found that higher HE4 levels were significantly associated with poorer survival 4,5 . However, these meta‐analyses only investigated the prognostic value of HE4 and did not analyze preoperative HE4 levels/expression in relation to postoperative pathologic factors, so the purpose of this meta‐analysis was to explore the relationship between HE4 expression in serum and tissue and postoperative pathological factors and prognosis.…”

MicroRNA-325-3p Targets Human Epididymis Protein 4 to Relieve Right Ventricular Fibrosis in Rats with Pulmonary Arterial Hypertension

“…Human epididymis protein 4 (HE4) has been reported to act as a fibroblast-derived mediator of renal fibrosis [ 10 , 11 ]. Zhang et al reported that hypoxia-induced HE4 promotes extracellular matrix accumulation and renal fibrosis [ 12 ].…”