[Gene expression profiling in prediction of tumor response to neoadjuvant concomitant chemoradiotherapy in patients with locally advanced rectal carcinoma: pilot study].

BACKGROUND: Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It can reduce tumor volume, thus increases a feasibility of sphincter-sparing surgery, shows less acute toxicity, improves local control rate. It is based on fluoropyrimidines (5-fluorouracil, capecitabine) with concurrent radiotherapy. The aim of the study was to evaluate the capability of gene expression method to identify nonresponders (NR) pretherapeutically. METHODS AND RESULTS: 17 patients with LARA, clinical stage II, III according to IUCC were enrolled into our pilot study. Response to therapy was determined clinically by transrectal ultrasonography and CT/MRI before and after therapy and histopathologically by TRG (tumor regression grade) according to Mandard. Patients with TRG 1-2 were included to responders group (R) and patients with TRG 4-5 composed NR group. Gene expression levels of 440 genes were obtained by low-density oligonucleotide microarrays. Gene expression data analysis based on SAM (Significance Analysis of Microarrays) and t-test methods identified 8 genes (RB1, RBBP4, HYOUI, JUNB, MDM4, CANX, MMP2, TCF7L2) significantly upregulated in NR. CONCLUSIONS: Validation of identified changes on the mRNA level (Real-Time PCR) and on protein level (immunohistochemistry) is ongoing. We suggest that low-density oligonucleotide microarray technology could contribute to individualize the therapy of patients with LARA.