Early dynamic transcriptomic changes during preoperative radiotherapy in patients with rectal cancer: A feasibility study

作     者：Stephane Supiot Wilfried Gouraud Loc Campion Pascal Jezéquel Bruno Buecher Josiane Charrier Marie-Francoise Heymann Marc-Andre Mahé Emmanuel Rio Michel Chérel 

作者机构：Department of Radiation OncologyInstitut de Cancérologie de l'Ouest René Gauducheau44800 Nantes-St-HerblainFrance INSERM U892Centre de Recherche en Cancérologie Nantes-AngersUniversity of Nantes44000 NantesFrance Centre Hospitalier Universitaire44000 NantesFrance Department of Nuclear MedicineInstitut de Cancérologie de l'Ouest René Gauducheau44800 Nantes-Saint HerblainFrance 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2013年第19卷第21期

页      面：3249-3254页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by Ligue Contre le Cancer  Programme Hospitalier de Recherche Clinique (20-R6) 

主　　题：CCL28 CLIC5 PDCD4 RAB27A TXNIP Protein metabolism Cell adhesion Cell migration SPON1 Carboxypeptidase E 

摘      要：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 (TT2, 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 ; PAB-PC1L ; TXNIP), signal transduction (CAPN5 ; F2RL2 ; RA- B27A ; 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 he