The Identification of Gut Neuroendocrine Tumor Disease by Multiple Synchronous Transcript Analysis in Blood
Open Access
- 15 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e63364
- https://doi.org/10.1371/journal.pone.0063364
Abstract
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are increasing in both incidence and prevalence. A delay in correct diagnosis is common for these lesions. This reflects the absence of specific blood biomarkers to detect NENs. Measurement of the neuroendocrine secretory peptide Chromogranin A (CgA) is used, but is a single value, is non-specific and assay data are highly variable. To facilitate tumor detection, we developed a multi-transcript molecular signature for PCR-based blood analysis. NEN transcripts were identified by computational analysis of 3 microarray datasets: NEN tissue (n = 15), NEN peripheral blood (n = 7), and adenocarcinoma (n = 363 tumors). The candidate gene signature was examined in 130 blood samples (NENs: n = 63) and validated in two independent sets (Set 1 [n = 115, NENs: n = 72]; Set 2 [n = 120, NENs: n = 58]). Comparison with CgA (ELISA) was undertaken in 176 samples (NENs: n = 81). 51 significantly elevated transcript markers were identified. Gene-based classifiers detected NENs in independent sets with high sensitivity (85–98%), specificity (93–97%), PPV (95–96%) and NPV (87–98%). The AUC for the NEN gene-based classifiers was 0.95–0.98 compared to 0.64 for CgA (Z-statistic 6.97–11.42, p2 = 12.3, p90%), identifies pancreatic and gastrointestinal NENs with similar efficacy, and confirms GEP-NENs when CgA levels are low. The panel is significantly more accurate than the CgA assay. This reflects its utility to identify multiple diverse biological components of NENs. Application of this sensitive and specific PCR-based blood test to NENs will allow accurate detection of disease, and potentially define disease progress enabling monitoring of treatment efficacy.This publication has 77 references indexed in Scilit:
- From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancerThe Journal of Pathology, 2012
- Circulating tumour markers can define patients with normal colons, benign polyps, and cancersBritish Journal of Cancer, 2011
- COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in CancerNucleic Acids Research, 2010
- k-Nearest neighbor models for microarray gene expression analysis and clinical outcome predictionThe Pharmacogenomics Journal, 2010
- Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19/mammaglobin RT–PCR in patients with metastatic breast cancerBritish Journal of Cancer, 2009
- Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learningCancer, 2009
- ArrayExpress update--from an archive of functional genomics experiments to the atlas of gene expressionNucleic Acids Research, 2009
- Gastroenteropancreatic neuroendocrine tumoursThe Lancet Oncology, 2008
- Genetic Differentiation of Appendiceal Tumor MalignancyAnnals of Surgery, 2006
- Gene expression profiling predicts clinical outcome of breast cancerNature, 2002