A meta-analysis of the accuracy of a neuroendocrine tumor mRNA genomic biomarker (NETest) in blood

Ann Oncol. 2020 Feb;31(2):202-212. doi: 10.1016/j.annonc.2019.11.003. Epub 2019 Dec 20.


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.

Keywords: IVD; NETest; biomarker; liquid biopsy; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Genomics
  • Humans
  • Liquid Biopsy
  • Neuroendocrine Tumors* / diagnosis
  • Neuroendocrine Tumors* / genetics
  • RNA, Messenger


  • Biomarkers, Tumor
  • RNA, Messenger