ABSTRACT

Objectives: Serum biomarkers are valuable for clinical decision-making for patients with hepatocellular carcinoma (HCC), among which the most promising are AFP, AFP-L3, DCP, DKK-1, and GP73; however, the efficacy of using combined biomarkers remains controversial. This meta-analysis provides insights regarding this topic.

Methods: After systematically surveying the literature available in PubMed, Embase, and Cochrane Library, we identified 28 qualified articles published since January 2015. A random-effects model was used to assess pooled sensitivity, specificity, positive and negative likelihood ratios (PLRs and NLPs), and diagnostic odds ratio (DOR).

Results: Values under the summary receiver operating characteristic (SROC) curve varied in different panels of the five biomarkers. Importantly, the sum of sensitivity and specificity of AFP+GP73 was 1.76 (P= 0.0001), which was the best among all the panels. The sum of the triple biomarker panel of AFP, AFP-L3, and DCP was larger (1.64, P= 0.0001) than those of any double biomarker panels of AFP, AFP-L3, and DCP.

Conclusions: To the best of our knowledge, this is the first meta-analysis to focus solely on combination assays of multiple biomarkers in HCC. The combined assay of AFP and GP73 conferred the best outcome among all panels. The triple combined panel of AFP, AFP-L3, and DCP showed higher diagnostic potential than individual random double combinations of the three biomarkers. Multiple-biomarker combined assays will be clinically important for decision-making processes for HCC.

摘要

目的：血清生物标志物对肝细胞癌（HCC）患者的临床决策具有重要价值，其中最有希望的是AFP、AFP-L3、DCP、DKK-1和GP73；然而，使用联合生物标志物的疗效仍存在争议。该荟萃分析提供了有关该主题的见解。

方法：在系统地调查 PubMed、Embase 和 Cochrane 图书馆中可用的文献后，我们确定了自 2015 年 1 月以来发表的 28 篇合格文章。使用随机效应模型评估汇总的敏感性、特异性、阳性和阴性似然比（PLR 和 NLP ) 和诊断优势比 (DOR)。

结果：汇总接受者操作特征 (SROC) 曲线下的值在五种生物标志物的不同组中有所不同。重要的是，AFP+GP73 的敏感性和特异性之和为 1.76（P=0.0001），是所有组中最好的。AFP、AFP-L3 和 DCP 三重生物标志物组的总和大于 (1.64, P = 0.0001) 比 AFP、AFP-L3 和 DCP 的任何双生物标志物组的总和更大 (1.64, P = 0.0001)。

结论：据我们所知，这是第一个仅关注 HCC 中多种生物标志物联合检测的荟萃分析。AFP 和 GP73 的联合测定在所有组中赋予了最佳结果。AFP、AFP-L3 和 DCP 的三重组合面板显示出比三种生物标志物的单独随机双重组合更高的诊断潜力。多生物标志物联合检测对于 HCC 的决策过程在临床上具有重要意义。