New specific molecular targets for radio-chemotherapy of rectal cancer

Snipstad, Kristin; Fenton, Christopher G.; Kjæve, Jørn; Cui, Guanglin; Anderssen, Endre; Paulssen, Ruth H.

doi:10.1016/j.molonc.2009.11.002

« Previous Next »Molecular Oncology
Volume 4, Issue 1 , Pages 52-64, February 2010

New specific molecular targets for radio-chemotherapy of rectal cancer

Kristin Snipstad
- Laboratory of Molecular Medical Research, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway
- These authors contributed equally to this work.
Christopher G. Fenton
- Laboratory of Molecular Medical Research, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway
- These authors contributed equally to this work.
Jørn Kjæve
- Department of Gastric Surgery, University Hospital of North-Norway, N-9038 Tromsø, Norway
Guanglin Cui
- Laboratory of Molecular Medical Research, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway
Endre Anderssen
- Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7006 Trondheim, Norway
Ruth H. Paulssen
- Laboratory of Molecular Medical Research, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway
- Corresponding author. Tel.: +47 776 45480.

Received 13 August 2009; received in revised form 10 November 2009; accepted 13 November 2009. published online 27 November 2009.

Abstract

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.