He Yong-Peng, Li Li-Xian, Tang Jia-Xi, Yi Lin, Zhao Yi, Zhang Hai-Wei, Wu Zhi-Juan, Lei Hai-Ke, Yu Hui-Qing, Nian Wei-Qi, Gan Lin
Department of Biochemistry and Molecular Biology, College of Basic Medical sciences, Southwest Medical University, Luzhou.
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.
Medicine (Baltimore). 2019 Sep;98(39):e17198. doi: 10.1097/MD.0000000000017198.
The aim of our study was to assess the value of serum human epididymis protein 4 (HE4) to diagnose lung cancer and provide reliable scientific conclusions to guide clinical practice.
A systematic search of the PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, and WANFANG databases was conducted to identify all studies examining serum HE4 in the diagnosis of lung cancer published up to June, 2017. The Quality Assessment of Diagnostic Accuracy Studies tool was used to evaluate the methodological quality of each trial. The meta-analysis was performed using STATA software and Review Manager 5.3.
There were 21 studies involving 1883 cases and 1696 controls included in our meta-analysis. The pooled sensitivity and specificity of HE4 for diagnosing lung cancer were 0.73 (95% confidence interval [CI] 0.68-0.78) and 0.86 (95% CI 0.81-0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.4 (95% CI 3.8-7.5) and 0.31 (95% CI 0.26-0.37), respectively. The diagnostic odds ratio was 17 (95% CI 12-26). The area under the curve of the summary receiver-operating characteristic curve was 0.86 (95% CI 0.83-0.89). Race, assay method, type of cancer, sample size, and publication date might be sources of heterogeneity in our meta-analysis. Subgroup analyses showed that the sensitivity in Caucasians was higher than that in Asians (0.81, 95% CI 0.71-0.91; and 0.71, 95% CI 0.66-0.77, respectively), but the specificity in Asians was better than that in Caucasians (0.87, 95% CI 0.81-0.92; and 0.85, 95% CI 0.73-0.97, respectively). The chemiluminescent microparticle immunoassay had the highest sensitivity, with 0.79 (95% CI 0.73-0.97), and the enzyme-linked immunosorbent assay had the highest specificity, with 0.87 (95% CI 0.79-0.94). HE4 had high diagnostic efficacy when screening for small cell lung cancer with the highest specificity (0.90, 95% CI 0.77-1.00).
HE4 is a relatively promising and effective biomarker for the diagnosis of lung cancer. Furthermore, given the limitations of our study, additional large-scale and well-designed studies are needed in the future.
我们研究的目的是评估血清人附睾蛋白4（HE4）在诊断肺癌中的价值，并提供可靠的科学结论以指导临床实践。
系统检索了PubMed、EMBASE、Cochrane图书馆、中国知网、中国生物医学文献数据库和万方数据库，以识别截至2017年6月发表的所有关于血清HE4在肺癌诊断中的研究。使用诊断准确性研究质量评估工具评估每个试验的方法学质量。使用STATA软件和Review Manager 5.3进行荟萃分析。
我们的荟萃分析纳入了21项研究，涉及1883例病例和1696例对照。HE4诊断肺癌的合并敏感性和特异性分别为0.73（95%置信区间[CI]0.68 - 0.78）和0.86（95%CI 0.81 - 0.91）。阳性似然比和阴性似然比分别为5.4（95%CI 3.8 - 7.5）和0.31（95%CI 0.26 - 0.37）。诊断比值比为17（95%CI 12 - 26）。汇总受试者工作特征曲线下面积为0.86（95%CI 0.83 - 0.89）。种族、检测方法、癌症类型、样本量和发表日期可能是我们荟萃分析中异质性的来源。亚组分析表明，白种人的敏感性高于亚洲人（分别为0.81，95%CI 0.71 - 0.91；和0.71，95%CI 0.66 - 0.77），但亚洲人的特异性优于白种人（分别为0.87，95%CI 0.81 - 0.92；和0.85，95%CI 0.73 - 0.97）。化学发光微粒子免疫分析具有最高的敏感性，为0.79（95%CI 0.73 - 0.97），酶联免疫吸附分析具有最高的特异性，为0.87（95%CI 0.79 - 0.94）。在筛查小细胞肺癌时，HE4具有较高的诊断效能，特异性最高（0.90，95%CI 0.77 - 1.00）。
HE4是一种相对有前景且有效的肺癌诊断生物标志物。此外，鉴于我们研究的局限性，未来需要更多大规模且设计良好的研究。
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