Assessment of differential gene expression patterns in human colon cancers

Objective To use a novel genomic approach to determine differential gene ex pression patterns in colon cancers of different metastatic potential. Summary Background Data Colorectal cancer is the third leading cause of can cer deaths in the United States; despite aggressive treatment strategies, t he 5-year survival rate for metastatic cancer has not changed in 50 years. The analysis of changes in gene expression patterns associated with metasta sis may provide new treatment strategies. Methods Human colon cancer cells KM12C (derived from a Dukes B colon cancer ), KML4A (a metastatic variant derived from KM12C), and KM20 (derived from a Dukes D colon cancer) were extracted for RNA. In addition, RNA was extrac ted from normal colon, primary cancer, and liver metastasis in a patient wi th metastatic colon cancer. Gene expression patterns for approximately 1,20 0 human genes were analyzed and compared by cDNA array techniques. Results Of the roughly 1,200 genes assessed in the KM cell lines, 9 genes w ere noted to have a more than threefold change in expression (either increa sed or decreased) in the more metastatic KML4A and KM20 cells compared with KM12C. Assessment of tissues from a patient with metastatic colon cancer d emonstrated a more than threefold change in the expression of 14 genes in t he primary cancer and liver metastasis compared with normal mucosa. Conclusions Using cDNA expression array technology, the authors identified genes with expression levels that are altered with metastasis. The ability to analyze and compare the expression patterns of multiple genes simultaneo usly provides a powerful technique to identify potential molecular targets for novel therapeutic strategies.