BACKGROUND The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy-liquid biopsy-to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). PATIENTS AND METHODS A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was undertaken. The methodological quality was evaluated using the QUADAS-2 tool. We identified ten original scientific papers that met the inclusion criteria. These were assessed by qualitative analysis and thereafter meta-analysis. Data were pooled and a median [95% confidence interval (CI)] diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. For the meta-analysis, a generic inverse variance method was undertaken using the accuracy and area under the curve (AUC) data. RESULTS The ten studies exhibited moderate to high methodological quality. They evaluated NETest usage both as a diagnostic and as a monitoring tool. The meta-analysis identified the diagnostic accuracy of the NETest to be 95%-96% with a mean DOR of 5 853, +LR of 195, and -LR of 0.06. The NETest was 84.5%-85.5% accurate in differentiating stable disease from progressive disease. As a marker of natural history, the accuracy was 91.5%-97.8%. As an interventional/response biomarker, the accuracy was 93.7%-97.4%. The pooled AUC for the NETest was 0.954 ± 0.005, with a z-statistic of 175.06 (P < 0.001). CONCLUSIONS The NETest is an accurate biomarker suitable for clinical use in NET disease management. The meta-analysis supports the utility of the NETest as an IVD to establish a diagnosis and monitor therapeutic efficacy. The use of this as a biomarker provides information relevant to NET management consistent with observations regarding utility of liquid biopsies in other oncological disciplines.

中文翻译：

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对血液中神经内分泌肿瘤 mRNA 基因组生物标志物 (NETest) 准确性的荟萃分析。

背景在神经内分泌肿瘤（NET）疾病中缺乏准确的血液生物标志物阻碍了管理。基因组医学的进步和分子生物标志物的发展提供了一种策略——液体活检——以促进实时管理。我们回顾了基于血液 mRNA 的 NET 生物标志物 NETest 作为体外诊断 (IVD) 的作用。患者和方法 使用系统评价和荟萃分析的首选报告项目 (PRISMA) 指南对文献进行系统评价。使用 QUADAS-2 工具评估方法学质量。我们确定了十篇符合纳入标准的原创科学论文。这些通过定性分析和随后的荟萃分析进行评估。汇总数据和中位数 [95% 置信区间 (CI)] 诊断优势比 (DOR)，计算阳性似然比（+LR）和阴性似然比（-LR）。对于荟萃分析，使用精度和曲线下面积 (AUC) 数据进行通用逆方差方法。结果 十项研究显示出中等到高的方法学质量。他们评估了 NETest 作为诊断和监控工具的使用情况。荟萃分析确定 NETest 的诊断准确性为 95%-96%，平均 DOR 为 5 853，+LR 为 195，-LR 为 0.06。NETest 在区分稳定疾病和进行性疾病方面的准确率为 84.5%-85.5%。作为自然史的标志物，准确率为91.5%-97.8%。作为介入/反应性生物标志物，准确率为93.7%-97.4%。NETest 的汇总 AUC 为 0.954 ± 0.005，z 统计量为 175.06 (P < 0.001)。结论 NETest 是一种准确的生物标志物，适用于 NET 疾病管理的临床应用。荟萃分析支持将 NETest 作为 IVD 用于建立诊断和监测治疗效果。将其用作生物标志物提供了与 NET 管理相关的信息，与液体活检在其他肿瘤学科中的效用观察结果一致。