Blood and tissue neuroendocrine tumor gene cluster analysis correlate, define hallmarks and predict disease status
- 2 June 2015
- journal article
- Published by Bioscientifica in Endocrine-Related Cancer
- Vol. 22 (4), 561-575
- https://doi.org/10.1530/erc-15-0092
Abstract
A multianalyte algorithmic assay (MAAA) identifies circulating neuroendocrine tumor (NET) transcripts (n=51) with a sensitivity/specificity of 98%/97%. We evaluated whether blood measurements correlated with tumor tissue transcript analysis. The latter were segregated into gene clusters (GC) that defined clinical ‘hallmarks’ of neoplasia. A MAAA/cluster integrated algorithm (CIA) was developed as a predictive activity index to define tumor behavior and outcome. We evaluated three groups. Group 1: publically available NET transcriptome databases (n=15; GeneProfiler). Group 2: prospectively collected tumors and matched blood samples (n=22; qRT-PCR). Group 3: prospective clinical blood samples,n=159: stable disease (SD):n=111 and progressive disease (PD):n=48. Regulatory network analysis, linear modeling, principal component analysis (PCA), and receiver operating characteristic analyses were used to delineate neoplasia ‘hallmarks’ and assess GC predictive utility. Our results demonstrated: group 1: NET transcriptomes identified (92%) genes elevated. Group 2: 98% genes elevated by qPCR (fold change >2,PR2=0.7,PP92%. Blood transcript measurement predicts NET activity.Keywords
This publication has 58 references indexed in Scilit:
- Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarkerWorld Journal of Gastroenterology, 2015
- Analytic and Clinical Validation of a Prostate Cancer–Enhanced Messenger RNA Detection Assay in Whole Blood as a Prognostic Biomarker for SurvivalEuropean Urology, 2014
- Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1Nature Communications, 2013
- The prognostic value of apoptotic and proliferative markers in breast cancerBreast Cancer Research and Treatment, 2013
- The genomic landscape of small intestine neuroendocrine tumorsJCI Insight, 2013
- STRING v9.1: protein-protein interaction networks, with increased coverage and integrationNucleic Acids Research, 2012
- Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine TumorsPLOS ONE, 2010
- Stability and aggregation of ranked gene listsBriefings in Bioinformatics, 2009
- Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learningCancer, 2009
- Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCRBiotechnology Letters, 2006