Prediction of sensitivity of locally advanced rectal adenocarcinomas to neoadjuvant combined therapy with fluoropyrimidines and concomitant radiotherapy by low-density oligonucleotide arrays

SLABÝ, Ondřej, Ingrid GARAJOVÁ, Marek SVOBODA, Eva KREJČÍ, Tamara ŠMERDOVÁ, Dana KNOFLÍČKOVÁ, Miroslav SVOBODA, Ilona KOCÁKOVÁ, Roman ŠEFR, Jana RŮŽIČKOVÁ, Pavel ŠLAMPA, Jiří HOCH a Rostislav VYZULA. Prediction of sensitivity of locally advanced rectal adenocarcinomas to neoadjuvant combined therapy with fluoropyrimidines and concomitant radiotherapy by low-density oligonucleotide arrays. In 3rd Symposium & Workshop on Molecular Patology, Book of Abstracts. Olomouc: UP Olomouc, 2007, s. 29-29. ISBN 978-80-244-1677-9.

Základní údaje

Originální název

Prediction of sensitivity of locally advanced rectal adenocarcinomas to neoadjuvant combined therapy with fluoropyrimidines and concomitant radiotherapy by low-density oligonucleotide arrays

Název česky

Predikce senzitivity lokálně pokročilého karcinomu konečníku na neoadjuvantní kombinovanou protinádorovou léčbu s fluoropyrimidiny a konkomitantní radioterapií pomocí nízkohustotních oligonukleotidových DNA čipů

Název anglicky

Prediction of sensitivity of locally advanced rectal adenocarcinomas to neoadjuvant combined therapy with fluoropyrimidines and concomitant radiotherapy by low-density oligonucleotide arrays

Autoři

SLABÝ, Ondřej, Ingrid GARAJOVÁ, Marek SVOBODA, Eva KREJČÍ, Tamara ŠMERDOVÁ, Dana KNOFLÍČKOVÁ, Miroslav SVOBODA, Ilona KOCÁKOVÁ, Roman ŠEFR, Jana RŮŽIČKOVÁ, Pavel ŠLAMPA, Jiří HOCH a Rostislav VYZULA

Vydání

Olomouc, 3rd Symposium & Workshop on Molecular Patology, Book of Abstracts, od s. 29-29, 1 s. 2007

Nakladatel

UP Olomouc

---

Další údaje

Jazyk

čeština

Typ výsledku

Stať ve sborníku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Lékařská fakulta

ISBN

978-80-244-1677-9

Klíčová slova anglicky

colorectal cancer; DNA microarray technology; gene expression; pathogenesis; prediction

Štítky

Colorectal cancer, DNA microarray technology, GENE EXPRESSION, pathogenesis, Prediction

---

Anotace

V originále

PURPOSE: Rectal cancer prognosis is favorable for surcigally cured patients in early stages of disease. With increasing staging and lymph node positivity of the rectal cancer also local reccurence rates are increased (20 to 60%) and the surcigal intervention which is the major treatment modality is supplied by adjuvant or neoadjuvant chemoradiotherapy. Recently, neoadjuvant and concomitant administration of chemoradiotherapy is prefered because of its several advantages eg. less acute toxicity, increased radiosensitivity due to more oxygenated cells and mainly decrease of tumor volume (downstaging) allowing subsequent more conservative sphincter-sparing surgery. Unfortunately, only about one third of patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy have evidential benefit characterized by complete pathological remission (pCR: ypT0 ypN0) or only minimal microscopic residues. Molecular characterization of sensitive patients should assist to oncologists in treatment decision by selecting those patients who will have benefit from neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: Eleven patients with locally advanced rectal adenocarcinomas neoadjuvantly treated with combined therapy based on fluoropyrimidines and concomitant radiotherapy were included to our pilot study. After therapy were five patients characterized by complete pathological remission, tumors of another six patients were not affected by therapy and stage of disease remains unchanged. Surgical microexcisions of bioptic samples were done before initiation of therapy. Total RNA was extracted from each frozen tumor specimen and relative gene expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 11 rectal cancer samples. RESULTS: Gene expression data analysis based on SAM (Significance Analysis of Microarrays) and t-test methods identified 7 genes (anti-apoptotic lipocalin 2, oncogene JUNB, cell cycle regulator RB1, p53-binding protein MDM4, calnexin, peroxisome proliferator-activated receptor delta PPARD, mucinlike adhesion molecule CD24) with significantly up-regulated expression in primary tumors of patients with poor response to therapy. In subsequent cluster analysis this group of genes was able to discriminate good from poor response cases. CONCLUSION: Our preliminary data suggest that low-density oligonucleotide microarray technology should contribute to a better understanding of rectal cancer resistance at molecular level, and facilitate prediction of tumor response to concomitant chemoradiotherapy. Supported by IGA MZ CR NR/9076.

Anglicky

PURPOSE: Rectal cancer prognosis is favorable for surcigally cured patients in early stages of disease. With increasing staging and lymph node positivity of the rectal cancer also local reccurence rates are increased (20 to 60%) and the surcigal intervention which is the major treatment modality is supplied by adjuvant or neoadjuvant chemoradiotherapy. Recently, neoadjuvant and concomitant administration of chemoradiotherapy is prefered because of its several advantages eg. less acute toxicity, increased radiosensitivity due to more oxygenated cells and mainly decrease of tumor volume (downstaging) allowing subsequent more conservative sphincter-sparing surgery. Unfortunately, only about one third of patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy have evidential benefit characterized by complete pathological remission (pCR: ypT0 ypN0) or only minimal microscopic residues. Molecular characterization of sensitive patients should assist to oncologists in treatment decision by selecting those patients who will have benefit from neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: Eleven patients with locally advanced rectal adenocarcinomas neoadjuvantly treated with combined therapy based on fluoropyrimidines and concomitant radiotherapy were included to our pilot study. After therapy were five patients characterized by complete pathological remission, tumors of another six patients were not affected by therapy and stage of disease remains unchanged. Surgical microexcisions of bioptic samples were done before initiation of therapy. Total RNA was extracted from each frozen tumor specimen and relative gene expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 11 rectal cancer samples. RESULTS: Gene expression data analysis based on SAM (Significance Analysis of Microarrays) and t-test methods identified 7 genes (anti-apoptotic lipocalin 2, oncogene JUNB, cell cycle regulator RB1, p53-binding protein MDM4, calnexin, peroxisome proliferator-activated receptor delta PPARD, mucinlike adhesion molecule CD24) with significantly up-regulated expression in primary tumors of patients with poor response to therapy. In subsequent cluster analysis this group of genes was able to discriminate good from poor response cases. CONCLUSION: Our preliminary data suggest that low-density oligonucleotide microarray technology should contribute to a better understanding of rectal cancer resistance at molecular level, and facilitate prediction of tumor response to concomitant chemoradiotherapy. Supported by IGA MZ CR NR/9076.

---

Návaznosti

NR9076, projekt VaV

Název: Genomické profilování v predikci odpovědi na chemoradioterapii u pacientů s lokálně pokročilým karcinomem konečníku