February 4, 2008

Molecular Pattern Linked to Colon Cancer Prognosis

Scanning electron micrograph of 5 cells spread on a surface Human colon cancer cells grown in the laboratory. Annie Cavanagh, Wellcome Images.

An international research team has linked levels of molecules called microRNAs to colon cancer progression. The finding may lead to new tools to assess colon cancer prognosis and help clinicians determine appropriate treatments. The researchers also uncovered a potential new target for colon cancer therapies.

MicroRNAs are small pieces of RNA that regulate how much of a protein is made. They do this by interfering with messenger RNA—the transient copies of genes that cells create as a template for building proteins. Scientists have only begun to understand the importance of microRNAs within the last decade, particularly in the context of cancer. In many types of tumors, the “expression levels” of several microRNAs—that is, the number of microRNAs made by the cell—are known to be altered.

A research team led by Dr. Curtis C. Harris at NIH’s National Cancer Institute (NCI) set out to examine microRNA expression profiles in people with colon adenocarcinoma. The team, including Dr. Carlo Croce at Ohio State University and Dr. S.Y. Leung at the University of Hong Kong in China, was supported by NCI and the Research Grants Council of the Hong Kong Special Administrative Region.

The researchers explained in the January 30, 2008, issue of the Journal of the American Medical Association that they used laboratory tools called microarrays to examine the levels of 389 microRNAs at once. They first studied the microRNA expression profiles of 84 colon adenocarcinoma patients in the United States, comparing their colon tumor tissue to adjacent, nontumorous tissue.

The scientists found that 37 microRNAs were expressed at different levels in tumors. Twenty-six were expressed at higher levels in tumors, with one called miR-21 enriched the most, at 1.8-fold. They then compared these expression levels with 5-year survival rates and found that 5 of the microRNAs, including miR-21, were associated with disease progression.

The researchers confirmed that the 5 microRNAs were expressed at higher levels in tumors by examining another group of 113 patients in Hong Kong. One of the microRNAs, miR-21, showed a strong association between expression and poor survival in both groups of patients. The researchers also found that, the more advanced the tumor, the higher the levels of miR-21 seemed to be. These findings suggest that miR-21 may play an important role in cancer development and progression.

Since microRNAs can be blocked with specifically designed inhibitors, miR-21 may prove to be a good therapeutic target. These 5 microRNAs could also be used to develop a prognostic tool for colon cancer.

NCI Director Dr. John Niederhuber said, “These findings hold great promise for improving our ability to determine, at the time of diagnosis, what a patient’s prognosis might be and the best course of therapy.”

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