title: The clinical utility of a novel blood-based multi-transcriptome assay for the diagnosis of neuroendocrine tumors of the gastrointestinal tract.
abstract: OBJECTIVE
  Current monoanalyte blood-based biomarkers for the diagnosis and follow-up of neuroendocrine tumors (NETs) do not achieve satisfactory metrics of sensitivity and specificity. We report the sensitivity and selectivity of the PCR-based test, the NETest, to detect tumors with reference to other benign and malignant gastrointestinal diseases.
  
  
  METHODS
  A total of 179 cases (gastrointestinal tumors: n=81; pancreatic disease: n=98) were prospectively collected and assessed using the NETest or chromogranin A (CgA) to determine metrics for detecting small intestinal and pancreatic NETs.
  
  
  RESULTS
  For intestinal carcinoids, the accuracy of the NETest was 93% (all NETs positive and 3 (12%) colorectal tumors were positive). CgA was positive in 80%, but 29% (n=7) of colorectal cancers were CgA positive. For pancreatic disease, the NETest accuracy was 94% (96% NETs positive, 2 (6%) of intraductal papillary mucinous neoplasms (IPMNs) were positive). The accuracy of CgA was 56% (29% of pancreatic NETs were CgA positive). Overall, the NETest was significantly more sensitive than CgA for the detection of small intestinal (area under the curve 0.98 vs. 0.75 P<0.0001) and pancreatic NETs (0.94 vs. 0.52, P<0.0001). NETest scores were elevated (P<0.05) in extensive disease and were more accurate (76-80%) than CgA levels (20-32%). The metrics of the multianalyte NETest met the performance criteria proposed by the National Institutes of Health for biomarkers, whereas CgA measurement did not.
  
  
  CONCLUSIONS
  This study demonstrates that a blood-based multianalyte NET gene transcript measurement of well-differentiated small intestinal and pancreatic neuroendocrine tumor disease is sensitive and specific and outperforms the current monoanalyte diagnostic strategy of plasma CgA measurement.
authors.affiliation: 1] Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA [2] Wren Laboratories, Branford, Connecticut, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Modlin
authors.affiliation: Wren Laboratories, Branford, Connecticut, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kidd
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bodei
authors.affiliation: Wren Laboratories, Branford, Connecticut, USA.
authors.forename: I
authors.initials: I
authors.lastname: Drozdov
authors.affiliation: Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA.
authors.forename: H
authors.initials: H
authors.lastname: Aslanian
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D010181:Pancreatic Cyst / Q000175:diagnosis; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests; D012372:ROC Curve; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A