Clinicopathological significance of the gene expression of matrix metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2 and insulin-like growth factor-1 receptor in patients with colorectal cancer: insulin-like growth factor-1 receptor gene expression is a useful predictor of liver metastasis from colorectal cancer.

Matrix metalloproteinase-7 (MMP-7), secreted by cancer cells, has been implicated classically in the basement membrane destruction associated with tumor cell invasion and metastasis. Epidemiological studies have established a correlation between high levels of circulating insulin-like growth factor-1 (IGF-1) and the relative risk of colorectal cancer, which is known to produce MMP-7. We examined the clinicopathological significance of the relative expression of MMP-7, IGF-1, IGF-2 and IGF-1 receptor genes in patients with colorectal cancer, especially with regard to metastasis. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal carcinoma. MMP-7, IGF-1, IGF-2, IGF-1R and beta-actin mRNA in cancer tissue and adjacent normal mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. MMP-7 and IGF-1R gene expression levels were higher in cancer tissue than in adjacent normal mucosa. In contrast, IGF-1 gene expression was lower in cancer tissue than in adjacent normal mucosa. As for the relationship of gene expression to clinicopathological factors, IGF-1R expression correlated with venous invasion and liver metastasis. IGF-1R gene expression is thus considered a useful predictor of liver metastasis from colorectal cancer.