|Researchers Identify Novel Molecular Pattern Linked to Colon Cancer Prognosis
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
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
"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."
For more information on Dr. Harris's laboratory, please
go to http://ccr.cancer.gov/staff/staff.asp?profileid=5761.
For more information about cancer, please visit the NCI Web site
or call NCI's Cancer Information Service at 1-800-4-CANCER
The most effective way to prevent colorectal cancer or detect
it early is to begin regular screening. For more information about
colorectal cancer screening, please visit the CDC website
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yeun ST, Chan TL, Kwong DLW, Au GKH, Liu C, Calin GA, Croce CM, and Harris CC. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinomas. JAMA, January 30, 2008, Vol. 299, No. 4.