Department of Obstetrics and Gynecology, Hebei General Hospital, Shijiazhuang, China.
Graduate School of Hebei Medical University, Shijiazhuang, China.
J Obstet Gynaecol Res. 2022 Sep;48(9):2255-2269. doi: 10.1111/jog.15356. Epub 2022 Jul 17.
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.
人附睾蛋白 4（HE4）与子宫内膜癌（EC）的预后之间的相关性尚未达成共识。因此，我们进行了一项荟萃分析，以评估 HE4 与 EC 预后之间的关系。
在这项系统评价和荟萃分析中，我们对数据库进行了搜索。通过比值比（OR）或标准化均数差（SMD）及其 95%置信区间（CI），分别确定血清或组织 HE4 与临床病理特征的相关性。使用风险比（HR）及其 95%CI 来评估 HE4 与生存结局之间的相关性。
共纳入 38 项已发表的研究。我们发现，高水平的血清 HE4 与 FIGO III-IV 期（SMD=1.58，95%CI：1.18-1.98，p<0.001）、G3 级（SMD=0.66，95%CI：0.39-0.93，p=0.001）、≥50%的子宫肌层浸润（SMD=0.78，95%CI：0.58-0.99，p<0.001）、脉管间隙浸润（SMD=0.82，95%CI：0.54-1.11，p=0.001）、淋巴结转移（SMD=1.27，95%CI：0.84-1.69，p<0.001）、宫颈侵犯（SMD=0.71，95%CI：0.43-0.98，p=0.003）、宫旁侵犯（SMD=1.03，95%CI：0.71-1.35，p<0.001）和腹腔细胞学（SMD=0.49，95%CI：0.22-0.75，p<0.001）显著相关。组织 HE4 高表达仅与淋巴结转移显著相关（OR=6.19，95%CI：2.07-18.50，p=0.001）。高水平的血清 HE4 与总生存不良（单因素：HR=3.77，95%CI：1.94-7.32，p<0.001；多因素：HR=2.15，95%CI：1.65-2.80，p<0.001）和无病生存不良（单因素：HR=2.89，95%CI：2.14-3.88，p<0.001；多因素：HR=2.31，95%CI：1.20-2.67，p<0.001）显著相关。与癌症抗原 125 相比，血清 HE4 可能是 EC 更好的预后指标。
HE4 高表达与 EC 的不良预后相关，可能是 EC 潜在的预后生物标志物。
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