A multianalyte algorithm PCR-based blood test outperforms single analyte ELISA-based blood tests for neuroendocrine tumor detection
Poster Mar 26, 2014
Mark Kidd, Irvin M Modlin, Daniele Alaimo, Stephen Callahan, Nancy Teixiera, Lisa Bodei, Ignat Drozdov
A key issue in management of neuroendocrine tumors (NETs) is specific and sensitive biomarkers. Measurements of single analytes in blood are widely utilized but have significant limitations. We developed a 51 transcript blood NET signature and compared it with standard approaches.
Methods: The multigene signature was evaluated in prospectively collected NETs (n=41, 61% small intestinal, 50% metastatic, 44% under treatment). These were age (NETs: mean 56.9 years, range: 31-76; controls: mean 56.4, range: 33-75) and sex-matched (M:F 10:31) with controls (1:1). Samples were analyzed by 2-step PCR protocol and ELISAs: (DAKO-CgA), pancreastatin (CusaBio-PST) and neurokinin A (RayBiotech-NKA). Sensitivity comparisons included chi-square, non-parametric measurements and ROC analyses.
Results: The NETest identified thirty eight of 41 NETs with equivalent performance metrics: sensitivity/specificity 93% and an AUC of 0.96. For the single analyte ELISA assays, metrics ranged from 31-93% and AUCs from 0.55-0.67. The multigene transcript NETest significantly outperformed single analyte tests (Z-statistic=4.85-6.58, p<0.0001).
Conclusions: A 51 panel multigene blood transcript analysis is significantly more sensitive and efficient (>93%) than any single analyte assay (CgA, PST or NKA) for NET detection. Our data indicate that a blood-based multigene analytic measurement will provide increased sensitivity and specificity in minimally invasive disease detection.
P450 Induction in Cryopreserved Hepatocytes from PXR and CAR Nuclear Receptor Knock-out RatsPoster
The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of phase I (cytochrome P450s), phase II metabolizing enzymes and transporter genes in response to xenobiotics, including prescription drugs.READ MORE
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
A new method for generating arrayed RNAi screening tools for any organismPoster
RNA interference (RNAi) using small interfering RNAs (siRNAs) is an important technology for down-regulation of gene expression and a powerful tool to study cellular processes and pathways. Previously, large collections of siRNAs were available only for traditional experimental model systems, such as human and mouse, and predominantly provided as chemically synthesized libraries.READ MORE
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