Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications

The WISPs (Wm-inducted secreted proteins. WISP-1. WISP-2 and WISP-3) are part of the CCN family These molecules are known to play a diverse role in cells but their role in cancer cells remains controversial. We analysed the expression of the three WISP molecules at the mRNA and protein levels in a cohort of 94 human colorectal tumours and 80 normal colorectal tissues and correlated the results with the pathological features and clinical outcome of the patients. WISP-I transcripts were found at higher levels in the. tumour samples than in the normal tissue (p=0 0015): higher in patients with Dukes stage B and C compared to Dukes A (p=0.017 and p=0.024, respectively), higher in patients with moderately and poorly differentiated cancers compared to the well differentiated cancers (p=0.020 and p=0 076, respectively and p=0 0035 when combined): higher in node positive tumours compared with the node negative (p=0 11) and in the patients with higher TNM staging (TNM 2, 3 and 4 compared to TNM 1 p=0.037). WISP-2 showed the opposite pattern with lower levels of expression in cancer cells compared to normal (p=0 082). Although no significant differences were found within the cancer group when indices of a more aggressive tumour were compared to the normal tissue a significant reduction in expression was found (I)Likes C p=0 044. poorly differentiated p=0.019, TNM 3 p=0.020 and node, positive disease p=0.048) WISP-3 transcript levels showed no significant differences between groups WISPs may play important but contrasting roles in colorectal cancer with WISP-1 appearing to act as a factor stimulating aggressiveness. WISP-2 as a tumour suppressor and WISP-3 having no definable beneficial or detrimental role.