J 2014

Test of Four Colon Cancer Risk-Scores in Formalin Fixed Paraffin Embedded Microarray Gene Expression Data

NARZO, Antonio Fabio Di, Sabine TEJPAR, Simona ROSSI, Pu YAN, Vlad POPOVICI et. al.

Basic information

Original name

Test of Four Colon Cancer Risk-Scores in Formalin Fixed Paraffin Embedded Microarray Gene Expression Data

Authors

NARZO, Antonio Fabio Di, Sabine TEJPAR, Simona ROSSI, Pu YAN, Vlad POPOVICI, Pratyaksha WIRAPATI, Eva BUDINSKÁ, Tao XIE, Heather ESTRELLA, Adam PAVLICEK, Mao MAO, Martin ERIC, Weinrich SCOTT, Fred T BOSMAN, Arnaud ROTH and Mauro DELORENZI

Edition

Journal of the National Cancer Institute, Bethesda, National Cancer Institute, 2014, 0027-8874

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 12.583

Organization unit

Faculty of Medicine

Keywords in English

colon cancer; microarray; gene expression; prognostic signature

Tags

Změněno: 6/5/2016 13:45, Ing. Mgr. Věra Pospíšilíková

Abstract

V originále

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.