A PCR blood test outperforms chromogranin A in carcinoid detection and is unaffected by proton pump inhibitors
Open Access
- 1 December 2014
- journal article
- Published by Bioscientifica in Endocrine Connections
- Vol. 3 (4), 215-223
- https://doi.org/10.1530/ec-14-0100
Abstract
A critical requirement in neuroendocrine tumor (NET) management is a blood biomarker test that is sensitive, specific and reproducible. We evaluated a PCR-based 51-transcript signature to detect tumors, compared it with chromogranin A (CgA) and examined the confounding effect of proton pump inhibitors (PPIs), which cause falsely elevated CgA levels. The multigene signature was evaluated in two groups. Group 1: 125 prospectively collected NETs: gastroenteropancreatic NETs (n=91, including 42 pancreatic and 40 small intestinal), carcinoids of unknown primary (n=18) and other sites (n=16). Group 2: prospectively collected non-NET patients receiving PPIs (>1 month; dyspepsia, n=19; GERD, n=6; and pancreatitis, n=4) and 50 controls. All samples were analyzed by PCR (marker genes) and ELISA (DAKO–CgA). Sensitivity comparisons included χ2, non-parametric measurements, and receiver operating characteristic (ROC) curves. Group 1: 123 NETs were PCR-positive (98.4%) compared with 50 (40%) CgA-positive (χ2=97.3, P−26). Significant differences (PP−9) and small intestine: 100 vs 58% (P−4). The multigene test was elevated in all grades (G1–G3), in both local and disseminated disease, and was not normalized by somatostatin analog therapy. It was also elevated in 97% of CgA normal NETs. Group 2: PPI administration increased CgA in 83% and CgA was elevated in 26% of controls. PCR values were not elevated in either group. PCR performance metrics were as follows: sensitivity 98.4%, specificity 100%, positive predictive value 100%, negative predictive value 97.8%, and the ROC-derived area under the curve (AUC) was 0.997. These were significantly better than CgA (all metrics Z-statistic, 10.44, PKeywords
This publication has 42 references indexed in Scilit:
- Evaluation of a Multiplex Assay for Estimation of HIV-1 IncidencePLOS ONE, 2013
- The Identification of Gut Neuroendocrine Tumor Disease by Multiple Synchronous Transcript Analysis in BloodPLOS ONE, 2013
- Prevalence and Associations of the Use of Proton-Pump Inhibitors in Nursing Homes: A Cross-Sectional StudyJournal of the American Medical Directors Association, 2013
- Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assaysClinical Endocrinology, 2012
- Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine TumorsGastroenterology, 2008
- Priorities for Improving the Management of Gastroenteropancreatic Neuroendocrine TumorsJNCI Journal of the National Cancer Institute, 2008
- Systematic Evaluation of Candidate Blood Markers for Detecting Ovarian CancerPLOS ONE, 2008
- Gastroenteropancreatic neuroendocrine tumoursThe Lancet Oncology, 2008
- An Italian program of External Quality Control for chromogranin A (CgA) assay: performance evaluation of CgA determinationcclm, 2007
- Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCRBiotechnology Letters, 2006