The molecular mediators in colorectal cancer invasion.
Colorectal cancers exhibit infiltrative and pushing growth patterns, with the infiltrative phenotype having a worse prognosis. Oligonucleotide microarray analysis has been used on laser captured epithelial cells from the invasive margin of infiltrative and pushing cancers. This has identified 23 differentially expressed genes. Several of these genes are involved in tumour glycolysis, indicating that infiltrative cancers had a genetic profile favouring anaerobic metabolism. Other differentially expressed genes are those involved in cell cycle regulation, including cyclin D2 and the retinoblastoma gene. Cyclin D2 is increased at the invasive margin and is predictive of recurrence and survival. However, cyclin D2 expression appears to be independent of proliferative activity. These two areas form the basis for our current laboratory research activity. This is partly funded by a recent YCR grant.
Other research interests include investigations into laparoscopic surgery for colorectal cancer as part of the MRC CLASICC trial, lead by Professor PJ Guillou. We are also collaborating with the Dept of Robotics and Mechanical Engineering at the University of Leeds to develop an intracorporeal robot to assist laparoscopic surgery and as a delivery system for anticancer therapies. This work has recently been awarded NEAT (New and Emerging Application of Technology) funding.
Figure 1. The two invasive phenotypes of colorectal cancer: A pushing growth pattern B infiltrative growth pattern
Figure 2. Kaplain-Meier survival curves illustrating worse outcome in cyclin D2 positive colorectal cancers
Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AHM, Heath RM, Brown JM. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC Trial): multicentre, randomised controlled trial. The Lancet 2005; 365:1718-1726
Jayne DG, Guillou PJ, Thorpe H, Quirke P, Copeland J, Smith AHM, Heath RM, and Brown JM. Randomized Trial of Laparoscopic-Assisted Resection of Colorectal Carcinoma: 3-Year Results of the UK MRC CLASICC Trial Group. J Clin Oncology 2007; 25: 3061-68
Taylor GW, Jayne DG Robotic applications in abdominal surgery: their limitations and future developments. IJMRCAS 2007; 3(1): 3-9.