Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar 1;25(7):773-80.
doi: 10.1200/JCO.2006.07.4187.

Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan

Maguy Del Rio  1 , Franck Molina, Caroline Bascoul-Mollevi, Virginie Copois, Frédéric Bibeau, Patrick Chalbos, Corinne Bareil, Andrew Kramar, Nicolas Salvetat, Caroline Fraslon, Emmanuel Conseiller, Virginie Granci, Benjamin Leblanc, Bernard Pau, Pierre Martineau, Marc Ychou
Affiliations

Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan

Maguy Del Rio et al. J Clin Oncol. .

Abstract

Purpose: In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response.

Patients and methods: Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule.

Results: We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%.

Conclusion: After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.

PubMed Disclaimer

Figures

Fig 1
Fig 1
Analysis of gene signature by (A) unsupervised clustering and (B) principal component analysis (PCA). (A): column represents sample, and row represents gene. Red indicates relative high expression and green relative low expression. (B): PCA involves a mathematical procedure that represents the maximum of the data information by reducing the space dimension. Here 80% of the information was explained with the three principal components used in the graph.
Fig 2
Fig 2
Proportion of misclassification in validation sets as a function of the corresponding training set size. Solid line represents the misclassification rate which is equal to mean proportion obtained from 500 random training-validation sets. Dotted lines represent the 95% confidence intervals.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Weitz J, Koch M, Debus J, et al. Colorectal cancer. Lancet. 2005;365:153–65. - PubMed
    1. Vanhoefer U, Harstrick A, Achterrath W, et al. Irinotecan in the treatment of colorectal cancer: clinical overview. J Clin Oncol. 2001;19:1501–1518. - PubMed
    1. Pelley RJ. Oxaliplatin: a new agent for colorectal cancer. Curr Oncol Rep. 2001;3:147–155. - PubMed
    1. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355:1041–1047. - PubMed
    1. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30. - PubMed

Publication types

MeSH terms

Supplementary concepts