Brief Article
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World J Gastroenterol. Jun 7, 2013; 19(21): 3249-3254
Published online Jun 7, 2013. doi: 10.3748/wjg.v19.i21.3249
Early dynamic transcriptomic changes during preoperative radiotherapy in patients with rectal cancer: A feasibility study
Stephane Supiot, Wilfried Gouraud, Loïc Campion, Pascal Jezéquel, Bruno Buecher, Josiane Charrier, Marie-Francoise Heymann, Marc-Andre Mahé, Emmanuel Rio, Michel Chérel
Stephane Supiot, Marc-Andre Mahé, Emmanuel Rio, Department of Radiation Oncology, Institut de Cancérologie de l’Ouest René Gauducheau, 44800 Nantes-St-Herblain, France
Stephane Supiot, Wilfried Gouraud, Loïc Campion, Pascal Jezéquel, Josiane Charrier, Michel Chérel, INSERM U892, Centre de Recherche en Cancérologie Nantes-Angers, University of Nantes, 44000 Nantes, France
Bruno Buecher, Marie-Francoise Heymann, Centre Hospitalier Universitaire, 44000 Nantes, France
Michel Chérel, Department of Nuclear Medicine, Institut de Cancérologie de l’Ouest René Gauducheau, 44800 Nantes-Saint Herblain, France
Author contributions: Supiot S, Jezéquel P, Buecher B, Mahé MA and Chérel M designed the research; Supiot S, Jezéquel P and Chérel M performed the research; Supiot S, Buecher B, Charrier J, Heymann MF, Mahé MA, Rio E and Chérel M contributed new reagents and analytic tools; Supiot S, Gouraud W, Campion L, Jezéquel P, Heymann MF and Chérel M analyzed the data; Supiot S, Gouraud W, Campion L and Chérel M wrote the paper.
Supported by Ligue Contre le Cancer, Programme Hospitalier de Recherche Clinique (20-R6)
Correspondence to: Michel Chérel, PhD, INSERM U892, Centre de Recherche en Cancérologie Nantes-Angers, University of Nantes, 8 quai Moncousu - BP 70721, 44000 Nantes, France. michel.cherel@univ-nantes.fr
Telephone: +33-2-28080245 Fax: +33-2-28080204
Received: December 20, 2012
Revised: February 22, 2013
Accepted: March 21, 2013
Published online: June 7, 2013
Processing time: 166 Days and 19.3 Hours
Abstract

AIM: To develop novel biomarkers of rectal radiotherapy, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy.

METHODS: Six patients presenting with a locally advanced rectal cancer (T>T2, N0/Nx, M0) eligible for preoperative radiotherapy (45 Gy in 25 fractions) were selected in a pilot study. Six tumor and 3 normal tissues biopsies were taken before and during radiotherapy, after a dose of 7.2 Gy at a median time of 1 h following irradiation (0:27-2:12). Tumor or normal tissue purity was assessed by a pathologist prior to RNA extraction. Mean RNA content was 23 μg/biopsy (14-37) before radiotherapy and 22.7 μg/biopsy (12-35) during radiotherapy. After RNA amplification, biopsies were analysed with 54K HG-U133A Plus 2.0 Affymetrix expression micro-arrays. Data were normalized according to MAS5 algorithm. A gene expression ratio was calculated as: (gene expression during radiotherapy - gene expression before radiotherapy)/gene expression before radiotherapy. Were selected genes that showed a ratio higher than ± 0.5 in all 6 patients.

RESULTS: Microarray analysis showed that preoperative radiotherapy significantly up-regulated 31 genes and down-regulated 6 genes. According to the Gene Ontology project classification, these genes are involved in protein metabolism (ADAMDEC1; AKAP7; CAPN5; CLIC5; CPE; CREB3L1; NEDD4L; RAB27A), ion transport (AKAP7; ATP2A3; CCL28; CLIC5; F2RL2; NEDD4L; SLC6A8), transcription (AKAP7; CREB3L1; ISX; PABPC1L; TXNIP), signal transduction (CAPN5; F2RL2; RAB27A; TNFRSF11A), cell adhesion (ADAMDEC1; PXDN; SPON1; S100A2), immune response (CCL28; PXDN; TNFRSF11A) and apoptosis (ITM2C; PDCD4; PVT1). Up-regulation of 3 genes (CCL28; CLIC5; PDCD4) was detected by 2 different probes and up-regulation of 2 genes (RAB27A; TXNIP) by 3 probes.

CONCLUSION: Micro-arrays can efficiently assess early transcriptomic changes during preoperative radiotherapy for rectal cancer, and may help better understand tumor radioresistance.

Keywords: CCL28; CLIC5; PDCD4; RAB27A; TXNIP; Protein metabolism; Cell adhesion; Cell migration; SPON1; Carboxypeptidase E

Core tip: To develop novel biomarkers of radiotherapy for rectal cancer, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy in a pilot study. Microarray analysis showed that preoperative radiotherapy significantly up-regulated 31 genes and down-regulated 6 genes, involved in protein metabolism, ion transport, transcription, signal transduction, cell adhesion, immune response and apoptosis. Micro-arrays could efficiently assess early transcriptomic changes during preoperative radiotherapy for rectal cancer. This may help better understand tumor radioresistance.