Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene signature may improve colon cancer treatment

01.03.2010
A gene signature, first identified in mouse colon cancer cells, may help identify patients at risk of colon cancer recurrence, according to a recent study by Vanderbilt-Ingram Cancer Center researchers.

The findings, published in the March issue of Gastroenterology, could help personalize treatments for colon cancer — the second leading cause of cancer-related deaths in the United States — by identifying patients most likely to benefit from chemotherapy.

In its early stages, colorectal cancer is treated with surgery only. However, between 20 percent and 25 percent of patients with Stage II disease (when the tumor has penetrated the muscular wall of the colon) will experience metastatic recurrence after surgical resection alone.

For stage III, when the cancer has spread to the lymph nodes, surgery is generally followed by chemotherapy — despite research showing that about 40 percent of stage III patients treated by surgery alone do not have a recurrence of disease in five years.

This suggests that identifying stage II patients at the greatest risk for recurrence — and targeting adjuvant chemotherapy to them — could decrease recurrences in that group. In addition, those stage III patients at lowest risk, if prospectively identified, could avoid having potentially toxic chemotherapy.

Using a mouse colon cancer cell line, R. Daniel Beauchamp, M.D., the John Clinton Foshee Distinguished Professor of Surgery and chair of the Section of Surgical Sciences, and colleagues identified 300 genes that showed distinct patterns of expression related to their ability to invade into a gel-like matrix, a test that reflects the aggressiveness of cancer cells.

Statistical analysis, led by Yu Shyr, Ph.D., the Ingram Professor of Cancer Research and professor of Biostatistics, helped refine the initial set of 300 genes into a set of 34 genes that were most closely associated with metastasis and death in a set of human colon cancer samples from Vanderbilt patients.

The researchers then examined whether this 34-gene signature could predict recurrence and death in a larger patient population.

In colon cancer tissue samples from 177 patients from the H. Lee Moffitt Cancer Center in Tampa, Fla., the signature identified in the highly invasive mouse cells — the "high recurrence" (or "poor prognosis") signature — was associated with increased risk of recurrence and death across all stages of disease.

Among patients with stage II disease, those with the "poor prognosis" signature had a five-year mortality rate of 31 percent. However, no stage II patients with a "low recurrence" (or "good prognosis") signature died within the five-year period.

In patients with stage III disease, 38 percent of those with a "poor" signature died of their disease within five years, whereas only 10.7 percent of those with a "good" prognosis signature died within that time period.

"Across all stages, if patients had a 'poor' prognosis signature, then they would be five times more likely to have a recurrence of cancer than those with a 'good' prognosis signature," said Beauchamp.

But the most interesting finding, Beauchamp says, is the ability of this gene signature to identify the patients most likely to benefit from chemotherapy.

Among stage III patients with a "poor" prognosis signature, those who had received chemotherapy had a 36 percent cancer-related death rate. Those who did not receive chemotherapy had an 86 percent death rate.

"That tells us that patients with the ('poor' prognosis signature) probably benefited from chemotherapy," Beauchamp said. "And (patients with a 'good' prognosis signature) appeared to get no benefit from chemotherapy."

"This really feeds right into personalized cancer medicine…in identifying subgroups of patients that will benefit from one treatment versus another treatment modality, trying to target those patients that are most likely to benefit…and not exposing patients who are less likely to benefit with potentially toxic treatments," Beauchamp said.

"Ultimately this should lead to more individualized therapy for cancer patients."

The research was supported by grants from National Institutes of Health.

Melissa Marino | EurekAlert!
Further information:
http://www.vanderbilt.edu

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>