VYUŽITIE PROFILOV GÉNOVEJ EXPRESIE K STANOVENIU ODPOVEDI K NEOADJUVATNEJ KONKOMITANTNEJ CHEMORÁDIOTERAPII U PACIENTOV S KARCINÓMOM REKTA: PILOTNÁ ŠTÚDIA

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Title in English GENE EXPRESSION PROFILING IN PREDICTION OF TUMOR RESPONSE TO NEOADJUVANT CONCOMITANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED RECTAL CARCINOMA: PILOT STUDY
Authors

GARAJOVÁ Ingrid SLABÝ Ondřej SVOBODA Marek FABIAN Pavel SILÁK Jan ŠMERDOVÁ Tamara KOCÁK Ivo RŮŽIČKOVÁ Jana HOCH Jiří VYZULA Rostislav

Year of publication 2008
Type Article in Periodical
Magazine / Source Časopis lékařů českých
MU Faculty or unit

Faculty of Medicine

Citation
Field Oncology and hematology
Keywords neoadjuvant therapy fluoropyrimidines radiotherapy rectal adenocarcinomas gene expression profiling DNA arrays
Description Backgrounds: 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 was to evaluate the capability of gene expression signatures to identify nonresponders (NR) pretherapeutically. Patients, methods: 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. Results: Gene expression data analysis based on SAM (Significance Analysis of Microarrays) and t test methods identified 8 genes (RB1, RBBP4, HYOU1, JUNB, MDM4, CANX, MMP2, TCF7L2) significantly upregulated in NR. Conclusion: 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.

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