New specific molecular targets for radio-chemotherapy of rectal cancer.
Patients with locally advanced rectal cancer often receive preoperative radio-chemotherapy (RCT). The mechanisms of tumour response to radiotherapy are not understood. The aim of this study was to identify the effects of RCT on gene expression in rectal tumour and normal rectal tissue. For that purpose tissue samples from 21 patients with resectable adenocarcinomas were collected for use in whole genome-microarray based gene expression analysis. A factorial experimental design allowed us to determine the effect of RCT on tumour tissue alone by removing the effect of radiation on normal tissue. This resulted in 1327 differentially expressed genes in tumour tissue with p<0.05. In addition to known markers for radio-chemotherapy, a Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in gene sets associated with cell adhesion and leukocyte transendothelial migration. The profound change of cell adhesion molecule expression in rectal tumour tissue could either increase the risk of metastasis, or decrease the tumour's invasive potential.
Snipstad
Kristin
K
Laboratory of Molecular Medical Research, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway.
Fenton
Christopher G
CG
Kjaeve
Jørn
J
Cui
Guanglin
G
Anderssen
Endre
E
Paulssen
Ruth H
RH
D000230:Adenocarcinoma / Q000235:genetics / Q000532:radiotherapy*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011300:Preoperative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins