ColoPrint®: A Gene Expression Profile that Identifies Patients at High Risk of Metastasis

Recently many independent studies have demonstrated that molecular staging (or genomic profiling) holds promise in predicting the long-term outcome of any one individual based on the gene expression profile of their cancer at diagnosis. Inherent to this approach is the hypothesis that every cancer contains informative gene expression signatures that, at the time of diagnosis, can portend the biologic behavior over time. The power of using microarray gene analysis for predicting the prognosis of stage II and III colon cancer patients has been demonstrated in several clinical studies, validating the use of prognostic profiles for clinical management of colon cancer patients.  Agendia has developed a prognostic profile for colon cancer that is currently being commercialized into a diagnostic assay for clinical utilization (ColoPrint). The development path follows Agendia’s successful commercialization of MammaPrint; the first genomic profile to achieve the stringent FDA IVDMIA clearance and widely used in the clinic for the prognosis of recurrence in early stage breast cancer patients thereby helping physicians to make more personalized therapeutic recommendations for each individual.(1-6)

 

Using microarray technology and tumor classification methods, a subset of genes was identified that are predictive for the risk of recurrence of stage II and III colon cancer. In this study, tumor tissue from a training cohort of 128 patients was collected for the gene signature development. Median follow-up was 67.3 months (1.9 – 270 months) during which 35 patients experienced a recurrence of their disease. Gene expression was measured on Agilent 44K Whole Genome oligonucleotide microarrays. Through multivariable analysis, a subset of genes was developed that can identify patients at risk of development of distant metastases. This classifier (or prognostic profile) was applied to an independent validation cohort of 300 colon cancer patients with Stage II and III cancer with known follow-up collected at three independent cancer centers. In this patient cohort, approximately two-thirds were predicted to have a low risk with a false negative rate of ~8% (manuscript in preparation). In the training and validation set, the prognostic profile was more powerful than ASCO Guideline criteria for selecting high risk stage II patients.

 

Furthermore, multivariate analysis indicated that a combination of this classifier and selected clinical variables could prove even more powerful and accurate in identifying high risk patients. A more detailed comparison between the prognostic profile and clinical parameters will be addressed in the PARSC Clinical Trial for Early Stage Colon Cancer Patients.  In summary, ColoPrint identifies a subgroup of stage II and III patients with a high risk for recurrent disease who would most likely benefit from additional chemotherapy. 

 

Click here for more information on Agendia’s PARSC Clinical Trial for Stage II & III Colon Cancer Patients. 


References
1)  Eschrich S, Yang I, Bloom G et al. (2005) Molecular Staging for Survival Predication of Colorectal Cancer Patients. JCO 15;3526-35
2)  Barrier A, Boelle PY, Roser F et al. (2006) Stage II colon cancer prognosis prediction by tumor gene expression profiling. J Clin Oncol. 24(29):4685-91
3)  Lin YH, Friederichs J, Black MA et al. (2007) Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin Cancer Res. 13.498-507
4)  van 't Veer LJ, Dai H, van de Vijver MJ et al. (2002): Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530-536
5)  Buyse M, Loi S, van’t Veer LJ et al. (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer J Natl Cancer Inst. 98(17):1183-92
6)  Glas AM, Floore A, Delahaye LJ et al. (2006) Converting a breast cancer microarray signature into a high-throughput diagnostic test.  BMC Genomics. 2006 Oct 30;7:278