A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Irvin M. Modlin, Ignat Drozdov, Daniele Alaimo, Stephen Callahan, Nancy Teixiera, Lisa Bodei, Mark Kidd

Research output: Contribution to journalArticlepeer-review


A critical requirement in neuroendocrine tumor (NET) management is a sensitive, specific and reproducible blood biomarker test. We evaluated a PCR-based 51 transcript signature (NETest) and compared it to chromogranin A (CgA), pancreastatin (PST) and neurokinin A (NKA). The multigene signature was evaluated in two groups: i) a validation set of 40 NETs and controls and ii) a prospectively collected group of NETs (n=41, 61% small intestinal, 50% metastatic, 44% currently treated and 41 age-sex matched controls). Samples were analyzed by a two-step PCR (51 marker genes) protocol and ELISAs for CgA, PST and NKA. Sensitivity comparisons included χ2, non-parametric measurements, ROC curves and predictive feature importance (PFAI) analyses. NETest identified 38 of 41 NETs. Performance metrics were: sensitivity 92.8%, specificity 92.8%, positive predictive value 92.8% and negative predictive value 92.8%. Single analyte ELISA metrics were: CgA 76, 59, 65, and 71%; PST 63, 56, 59, and 61% and NKA 39, 93, 84, and 60%. The AUCs (ROC analysis) were: NETest: 0.96±0.025, CgA: 0.67±0.06, PST 0.56±0.06, NKA: 0.66±0.06. NETest significantly out-performed single analyte tests (area differences: 0.284-0.403, Z-statistic 4.85-5.9, P95% sensitivity and specificity, AUC Z0.98 vs single analytes: 59-67% sensitivity, AUCs: 0.58-0.63). The NETest is significantly more sensitive and efficient (>93%) than single analyte assays (CgA, PST or NKA) in NET diagnosis. Blood-based multigene analytic measurement will facilitate early detection of disease recurrence and can predict therapeutic efficacy.

Original languageEnglish
Pages (from-to)615-628
Number of pages14
JournalEndocrine-Related Cancer
Issue number4
Publication statusPublished - 2014


  • Biomarker
  • Carcinoid
  • Chromogranin A
  • Gastroenteropancreatic
  • Monoanalyte
  • Multianalyte
  • Multigene transcript
  • NET
  • Neuroendocrine
  • Neurokinin A
  • Pancreastatin
  • PCR
  • Proton pump inhibitor
  • PYY

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)


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