Jekyll-Hyde microRNA binding variant linked to improved outcome in early-stage colorectal cancer

October 28, 2010, American Association for Cancer Research

A variant site linked to poor outcome in advanced colorectal cancer has now been found to predict improved prognosis in early stages of cancer, according to research presented at the American Association for Cancer Research special conference on Colorectal Cancer: Biology to Therapy, held Oct. 27-30, 2010.

Researchers said they don't know why this variant site, a binding site that should allow appropriate regulation of the KRAS gene, exhibited a Dr. Jekyll and Mr. Hyde duality. Further study could show that patients with this miRNA variant might benefit from therapy early-on to forestall aggressive tumor behavior.

"Our results suggested that patients with this variant have a good prognosis, but only in early stages. We need to make sure we identify them in an early stage before the cancer progresses," said lead researcher Kim M. Smits, Ph.D., a molecular biologist and epidemiologist in the GROW-School for Oncology and Developmental Biology at Maastricht University Medical Center, in the Netherlands.

The binding site responds to a molecule that belongs to the lethal-7 (let-7) family of microRNAs that has been linked to control the KRAS gene, which, if unregulated or mutated, can lead to growth of colorectal cancers. But the "G" variant at this site has been shown to lead to poorly regulated KRAS because it does not allow appropriate binding of let-7 to the gene, thus leading to increased KRAS expression. The G variant has previously been associated with an increased risk of lung cancer in moderate smokers, increased risk of , reduced survival among patients with oral cancers and reduced survival in late-stage colorectal cancer independent of KRAS mutations.

In this study, the researchers evaluated the effect the G variant had on early-stage colorectal cancer compared to the more common "wild type" T variant.

Researchers examined preserved tissue from 409 early-stage colorectal cancer patients who were part of the Netherlands Cohort Study from 1989 to 1994. Median survival was 7.6 years, but patients with the G variant had a 54 percent improved survival compared to patients with T variant. This survival benefit was enhanced if KRAS mutations were taken into account, Smits said.

"None of the patients with a KRAS mutation and the T variant died," she said.

In later stages of the , this survival advantage was reversed, which Smits said was unexpected.

"You would intuitively think that the G variant would be associated with a poorer prognosis, as it is in late-stage , but that is not the case," said Smits.

Smits believes that in patients with the G variant, "KRAS control has been taken over by another, still unidentified pathway. These patients may be born with reduced KRAS control and I think the body has taken action on this, and another pathway controlling KRAS is overexpressed or activated to compensate for the imbalance."

"This would explain why these patients have a good prognosis, even if KRAS has an activating mutation — KRAS is controlled by another pathway," she said. "In late-stage patients, this alternative pathway might be impaired, thereby losing KRAS control."

Related Stories

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.