Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

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Serval ID
serval:BIB_7FE48BDA06AD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.
Journal
Journal of the National Cancer Institute
Author(s)
Di Narzo A.F., Tejpar S., Rossi S., Yan P., Popovici V., Wirapati P., Budinska E., Xie T., Estrella H., Pavlicek A., Mao M., Martin E., Scott W., Bosman F.T., Roth A., Delorenzi M.
ISSN
1460-2105 (Electronic)
ISSN-L
0027-8874
Publication state
Published
Issued date
2014
Volume
106
Number
10
Pages
1-8
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification.
METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase.
RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score.
CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.
Keywords
Adenocarcinoma/chemistry, Adenocarcinoma/mortality, Adult, Aged, Antineoplastic Agents/therapeutic use, Area Under Curve, Colonic Neoplasms/chemistry, Colonic Neoplasms/mortality, Disease-Free Survival, Female, Fixatives, Formaldehyde, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Recurrence, Local/mortality, Neoplasm Recurrence, Local/pathology, Neoplasm Staging, Paraffin, Predictive Value of Tests, Prognosis, Proportional Hazards Models, ROC Curve, Randomized Controlled Trials as Topic, Risk Assessment, Risk Factors, Tissue Array Analysis, Transcriptome, Treatment Failure, Tumor Markers, Biological/analysis
Pubmed
Web of science
Open Access
Yes
Create date
13/11/2014 18:31
Last modification date
25/09/2019 6:09
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