Gene Expression Profiling in Prediction of Tumor Response to Neoadjuvant Concomitant Chemoradiotherapy in Patients with Locally Advanced Rectal Carcinoma: Pilot Study
Authors:
I. Garajová 1,5; O. Slabý 2,5; M. Svoboda 1,5; P. Fabian 2; J. Silák 3; T. Šmerdová 2; I. Kocák 1; J. Růžičková 4; J. Hoch 6; R. Vyzula 1,5
Authors‘ workplace:
Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno
1; Oddělení onkologické a experimentální patologie, Masarykův onkologický ústav, Brno
2; Oddělení chirurgické onkologie, Masarykův onkologický ústav, Brno
3; Klinika radiační onkologie, Masarykův onkologický ústav, Brno
4; Lékařská fakulta, Masarykova univerzita, Brno
5; Chirurgická klinika 2. LF UK a FNM, Praha
6
Published in:
Čas. Lék. čes. 2008; 147: 381-386
Category:
Original Article
Overview
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, HYOU1, 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.
Key words:
neoadjuvant therapy, fluoropyrimidines, radiotherapy, rectal adenocarcinomas, gene expression profiling, DNA arrays.
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