Identification of molecular profiles and markers for response prediction in rectal cancer and their clinical application

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Preoperative 5-FU (5-fluorouracil)-based chemoradiotherapy (CT/RT) is recommended as standard therapy for UICC stage ll/lll rectal cancer in Germany. However, tumor response to preoperative CT/RT is very heterogeneous, ranging from complete response to resistance, and it remains unclear how the individual prognosis of patients will be affected by this treatment. We recently demonstrated that gene expression profiling can be useful for predicting response to preoperative CT/RT: 54 genes showed significantly different expression levels between responders and nonresponders. In a follow-up study, we were able to show that these 54 genes are also relevant for predicting local recurrence and disease-free survival. Within this subproject, we first aim to generate a customized microarray, which will contain this set of 54 genes as well as relevant genes analyzed within other subprojects, for prospective testing in a much larger cohort of patients. Second, we will perform a whole-genome screen to evaluate whether other genes might complement this gene set for response prediction. Third, the experiments in gene expression profiling will be complemented by a genome-wide screening for single nucleotide polymorphisms (SNPs) and changes in genomic copy numbers associated with response to chemoradiotherapy.