Neuroendocrine Tumor Omic Gene Cluster Analysis Amplifies the Prognostic Accuracy of the NETest.

Published on Jan 1, 2021in Neuroendocrinology4.271
· DOI :10.1159/000508573
Mark Kidd5
Estimated H-index: 5
,
Mark Kidd66
Estimated H-index: 66
+ 1 AuthorsIrvin M. Modlin81
Estimated H-index: 81
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Abstract
BACKGROUND: The NETest is a multi-gene assay comprising 51 circulating neuroendocrine tumor specific transcripts. The quotient of the 51-gene assay is based upon an ensemble of machine learning algorithms. Eight cancer hallmarks or "omes" (apoptome, epigenome, growth factor signalome, metabolome, proliferome, plurome, secretome SSTRome) represent 29 genes. The NETest is an accurate diagnostic (>90%) but its prognostic utility has not been assessed. In this study, we describe expansion of the NETest omic cluster components and demonstrate that integration amplifies NETest prognostic accuracy. METHODS: Group 1 (n=222; including stable disease (SD: n=164), progressive disease (PD: n=76) and controls (n=139)). Group 2: NET Registry #NCT02270567 (n=88, prospective samples (SD n=54 and PD n=34) with up to 24 months follow-up. We used PubMed literature review, interactomic analysis, non-parametric testing, Kaplan-Meier survival curves and Chi2 analyses to inform and define the prognostic significance of NET genomic "hallmarks". RESULTS: 2020 Analyses: In-depth analyses of 47 NETest genes identified a further 6 omes: fibrosome, inflammasome, metastasome, NEDome, neurome and TFome. Group 1 analysis: Twelve omes, excluding the inflammasome and apoptome, were significantly (p 2) versus SD. Group 2. All these 7 omes were upregulated. In PD, they were significantly more elevated (p 40) including the fibrosome/NEDome predicted PD development within 3 months (100%). Using decision tree analysis to integrate the 4 omes (epigenome, metastasome, fibrosome and NEDome) with the NETest score generated an overall prognostic accuracy of 93%. CONCLUSIONS: Examination of NETest omic gene cluster analysis identified 5 additional clinically-relevant cancer hallmarks. Identification of 7 omic clusters (septet) provides a molecular pathological signature of disease progression. The integration of the quartet (epigome, fibrosome, metastasome, NEDome) and the NETest score yielded a 93% accuracy in the prediction of future disease status.
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#1Irvin M. Modlin (Yale University)H-Index: 81
Last. Lisa Bodei (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
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ABSTRACT: null null Background null Biomarkers are key tools in cancer management. In neuroendocrine tumors (NETs), Chromogranin A (CgA) was considered acceptable as a biomarker. We assessed the clinical efficacy of a multigenomic blood biomarker (NETest) to CgA over a 5-year period. null null null Methods null An observational, prospective, cross-sectional, multicenter, multinational, comparative cohort assessment. Cohort #1: NETest evaluation in NETs (1,684) and cancers, benign diseases, contr...
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#1Irvin M. Modlin (Yale University)H-Index: 81
#2Mark KiddH-Index: 66
Last. Alexandra KitzH-Index: 2
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INTRODUCTION Identification of residual disease after neuroendocrine tumor (NET) resection is critical for management. Post-surgery imaging is insensitive, expensive and current biomarkers ineffective. We evaluated whether the NETest, a multigene liquid biopsy blood biomarker, correlated with surgical resection and could predict recurrence. METHODS Multicenter evaluation of NET resections over 24 months (n=103): 47 pancreas, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 stomach. Surgery: R0...
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#1Irvin M. Modlin (Yale University)H-Index: 81
#2Mark KiddH-Index: 66
Last. Alexandra KitzH-Index: 2
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Introduction Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods This was a multicenter ev...
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#1Anja Rinke (University of Marburg)H-Index: 22
#2Christoph J. Auernhammer (LMU: Ludwig Maximilian University of Munich)H-Index: 31
Last. Thomas M. Gress (University of Marburg)H-Index: 82
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Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) comprises clinically as well as prognostically diverse tumour entities often diagnosed at late stage. Current classification provides a uniform terminology and a Ki67-based grading system, thereby facilitating management. Advances in the study of genomic and epigenetic landscapes have amplified knowledge of tumour biology and enhanced identification of prognostic and potentially predictive treatment subgroups. Translation of this genomic a...
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#1Anna Malczewska (Medical University of Silesia)H-Index: 12
#2Kjell Öberg (Uppsala University Hospital)H-Index: 116
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Introduction The absence of a reliable, universal biomarker is a significant limitation in neuroendocrine neoplasia (NEN) management. We prospectively evaluated two CgA assays, (NEOLISA, EuroDiagnostica) and (CgA ELISA, Demeditec Diagnostics (DD)) and compared the results to the NETest. Methods NEN cohort (n = 258): pancreatic, n = 67; small intestine, n = 40; appendiceal, n = 10; rectal, n = 45; duodenal, n = 9; gastric, n = 44; lung, n = 43. Image-positive disease (IPD) (n = 123), image & hist...
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