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MicroRNAs May Predict Colon Cancer Prognosis

TUESDAY Jan. 29, 2008 -- Knowing whether or not a particular cancer will be aggressive allows doctors to more effectively treat their patients, and a newly found class of molecules called microRNAs may help doctors do just that.

Recent research has honed in on a particular microRNA, designated miR-21, that may predict outcomes in people with colon cancer. Tumor cells with high levels of miR-21 were associated with more than twice the risk of poor survival, according to a study in the Jan. 30 issue of the Journal of the American Medical Association.

"Progress is being made that is going to eventually lead to better diagnosis and predicting prognosis," said one of the study's authors, Dr. Curtis Harris, chief of the lab of human carcinogenesis at the U.S. National Cancer Institute in Bethesda, Md. "This is a new area of research that may develop exciting new therapies, but we're very early in the discovery phase. It's only been about five years since we've known about microRNA."

Colon cancer is the third most common type of cancer in the United States, and the second-leading cause of cancer death, according to background information in the study. Surgical removal of colon cancer is currently the only curative form of therapy, according to the study.

MicroRNA molecules are an attractive research target because they help control many cell functions -- from division to proliferation to apotosis (programmed cell death). They have also been implicated in the development of cancer. MicroRNA expression has been found to be altered in other malignancies, such as leukemia, lung cancer, and pancreatic cancer, the researchers said.

The researchers theorized that microRNA production was probably altered in colon cancer as well, and if they could isolate which microRNA was associated with poorer prognosis, this could eventually help clinicians decide who needs more aggressive treatment and who would likely do well with a less aggressive regimen.

For the study, the researchers examined colon cancer tumors and non-tumorous tissue from 84 people in the United States, looking specifically at microRNA expression. To validate the U.S. findings, Hong Kong researchers also examined tumors and non-tumorous tissues from 113 Chinese adults.

The scientists found that 37 microRNAs were expressed in different levels in the tumor tissue. However, only one -- miR-21 -- was statistically significantly associated with poorer outcome. MiR-21 was also found in precancerous tissues.

Tumors that expressed high levels of miR-21 were associated with a 2.5 times increased risk of poor survival in the U.S. group, and 2.4 times increase in the risk of poor survival outcomes for the Hong Kong group.

"These are two different clinical cohorts [groups of patients] that found a single microRNA could have prognostic significance," said William Phelps, scientific program director in the research department of the American Cancer Society.

"The association was not only associated with a less favorable outcome, but was also associated with a poorer response to therapy, independent of the stage of the tumor. This seems to suggest that miR-21 is a very early marker that predicts a poorer prognosis," Phelps said.

However, both Harris and Phelps said this study's findings need to be duplicated in a larger group and in different populations before they could be applied in practice to help predict how a particular cancer might behave.

More information

To learn more about colon cancer, visit the U.S. National Library of Medicine.

Posted: January 2008


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