An international research team has identified a link between the expression patterns of a class of molecules called microRNAs and how a patient's colon cancer may progress. These data, the first to make such a link, may lead to a new tool for clinicians to help them assess a colon cancer patient's prognosis and decide on appropriate treatment, while potentially providing a new target for the development of colon cancer therapies. The findings, by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), Ohio State University, and the University of Hong Kong, China, were published in the January 30, 2008, issue of the Journal of the American Medical Association. Additional research is planned to verify and build on these findings, which is needed before these results can be applied to tests or therapies in patients.
MicroRNAs are small pieces of RNA that regulate the transfer of information from genes into proteins. In particular, they are able to reduce or silence the expression of a particular gene by interfering with its messenger RNA -- the molecular go-between that carries instructions from the gene to the cell's protein-building machinery.
"The association between gene regulation systems, particularly microRNAs, and cancer is becoming stronger all the time," said NCI Director John Niederhuber, M.D. "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."
Genes for hundreds of microRNAs are contained within the human genome. Because they do not produce RNAs that encode proteins, their importance has only been recognized within the last decade, particularly in the context of cancer. MicroRNAs could potentially be able to help predict and lead to new drug development because their expression levels are altered in many types of tumors so they can be silenced with specifically designed inhibitors.
In this study, the research team, led by Curtis C. Harris, M.D., chief of the Laboratory of Human Carcinogenesis at NCI's Center for Cancer Research, compared microRNA expression profiles in tumor and adjacent healthy tissues from two groups of colon cancer patients, 84 in the United States and 113 in Hong Kong. Using genomic technologies, the researchers identified five microRNAs that were present in much greater amounts in colon cancer tumors than in normal tissues, and were associated with disease progression. The strong association between one microRNA in particular, called miR-21, and poor survival in both the U.S. and Hong Kong patient groups suggested that it warranted further study.
Subsequently, the scientists found that miR-21 expression tracked tumor stage -- the more advanced the tumor, the greater the amount of miR-21 present -- indicating that it may play a role in cancer development and progression and could, therefore, serve as a good drug development target. Comparisons of tumor stage, miR-21 expression, and clinical outcome in patients with stage II or III colon cancer also revealed associations between high levels of miR-21 and poor survival, poor therapeutic outcome, and, in patients who experienced a disease relapse, more rapid recurrence.
"To the best of our knowledge, this is the largest study done so far comparing microRNA profiles and clinical outcomes in colon cancer, and the only one to use tissues and data from two independent groups," Harris noted. These data build both a rationale for using expression of these five microRNAs as a prognostic tool in colon cancer and lend weight to a role for miR-21 in colon cancer development and treatment."
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