Sun Ming-Li, Yang Zhi-Yong, Wu Qi-Jun, Li Yi-Zi, Li Xin-Yu, Liu Fang-Hua, Wei Yi-Fan, Wen Zhao-Yan, Lin Bei, Gong Ting-Ting
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
Front Med (Lausanne). 2022 Mar 24;9:842002. doi: 10.3389/fmed.2022.842002. eCollection 2022.
The application of human epididymis protein 4 (HE4) in diverse health diseases, especially in cancers, has been extensively studied in recent decades. To summarize the existing evidence of the aforementioned topic, we conducted an umbrella review to systematically evaluate the reliability and strength of evidence regarding the role of HE4 in the diagnostic and prognostic estimate of diverse diseases.
Electronic searches in PubMed, Web of Science, and Embase databases were conducted from inception to September 16, 2021, for meta-analyses, which focus on the role of HE4 in the diagnosis and prognosis of diseases. This study protocol has been registered at PROSPERO (CRD42021284737). We collected the meta-analysis effect size of sensitivity, specificity, positive predictive value, and negative predictive value from diagnostic studies and gathered the hazard ratio () of disease-free survival, overall survival, and progression-free survival from prognostic studies. For each systematic review and meta-analysis, we used a measurable tool for evaluating systematic reviews and meta-analysis (AMSTAR) to evaluate the methodological quality. Additionally, we assessed the quality of evidence on estimating the ability of HE4 in the diagnosis and prognosis of diverse diseases by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline.
Overall, 20 meta-analyses including a total of 331 primary studies of different diseases were examined, mainly including ovarian cancer (OC) ( = 9), endometrial cancer (EC) ( = 6), and lung cancer (LC) ( = 4). The methodological qualities of all studies were rated as moderate (45%) or high (55%) by the AMSTAR. According to the GRADE, the certainties of 18 diagnostic pieces of evidence (9 for sensitivity and 9 for specificity) were rated as moderate (34%), low (33%), and very low (33%). Moreover, outcomes from prognosis studies showed evidence (1 for disease-free survival) with high certainty in regard to cancers (such as EC, OC, and LC) with the remaining three being moderate.
This umbrella review suggested that HE4 was a favored biomarker in the prognosis of cancers, which was supported by high certainty of evidence. Additionally, HE4 could provide a suitable method for the diagnosis of EC, OC, and LC with moderate certainty evidence. Further large prospective cohort studies are needed to better elucidate the diagnostic and prognostic role of HE4 in diseases.
近几十年来，人类附睾蛋白4（HE4）在多种健康疾病尤其是癌症中的应用得到了广泛研究。为总结上述主题的现有证据，我们进行了一项伞状综述，以系统评估关于HE4在多种疾病诊断和预后评估中作用的证据的可靠性和强度。
从数据库建立至2021年9月16日，在PubMed、Web of Science和Embase数据库中进行电子检索，查找聚焦于HE4在疾病诊断和预后中作用的荟萃分析。本研究方案已在国际前瞻性系统评价注册库（PROSPERO）注册（注册号：CRD42021284737）。我们从诊断研究中收集敏感性、特异性、阳性预测值和阴性预测值的荟萃分析效应量，并从预后研究中收集无病生存期、总生存期和无进展生存期的风险比（HR）。对于每项系统评价和荟萃分析，我们使用一种评估系统评价和荟萃分析的可测量工具（AMSTAR）来评估方法学质量。此外，我们根据推荐分级的评估、制定和评价（GRADE）指南评估关于HE4在多种疾病诊断和预后中评估能力的证据质量。
总体而言，共审查了20项荟萃分析，包括总共331项不同疾病的原始研究，主要包括卵巢癌（OC）（n = 9）、子宫内膜癌（EC）（n = 6）和肺癌（LC）（n = 4）。所有研究的方法学质量根据AMSTAR评定为中等（45%）或高（55%）。根据GRADE，18项诊断证据（9项敏感性证据和9项特异性证据）的确定性评定为中等（34%）、低（33%）和极低（33%）。此外，预后研究结果显示，对于某些癌症（如EC、OC和LC），无病生存期的证据确定性高，其余三项的证据确定性为中等。
这项伞状综述表明，HE4是癌症预后中一个受青睐的生物标志物，这得到了高确定性证据的支持。此外，HE4可以为EC、OC和LC的诊断提供一种证据确定性中等的合适方法。需要进一步开展大型前瞻性队列研究，以更好地阐明HE4在疾病中的诊断和预后作用。
