Absence of Transcriptomic Signature of Response to Chemotherapy in Metastatic Colorectal Carcinoma Patients

Abstract

Tumor gene-expression profiling may define signatures capable of discriminating between responders and nonresponders to chemotherapy. Fifty seven metastatic colorectal cancer patients were prospectively included and 40 tumors were analyzed. Patients were treated in first line with 5-fluorouracil associated with irinotecan or oxaliplatin. Response was evaluated using WHO criteria every 2 months after chemotherapy. Gene-expression profiling was performed using Applied Biosystems microarrays (Human Genome Survey Microarray v2.0; Paris, France). Data were analyzed using Bioconductor packages. Differential-expression analysis was performed by fitting a linear model. Moderated t-statistics were computed and p-values were adjusted for false-discovery rate. Pearson correlations tests were evaluated between gene expression and progression-free and overall survival. Nonsupervised analysis did not show any clustering of expression levels according to treatment response. Supervised analysis compared expression levels between responders and nonresponders, within each treatment group and independently from treatment. No genes were identified as differentially expressed at a p-value of 10(-3) and false-discovery rate of 30%. No correlation between expression levels and survival data was found. These negative results show that the determinants of response to chemotherapy should be sought not only in the tumor characteristics, but also among the processes leading to drug availability to the tumor.