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AROUND THE MEDICAL CENTER :: WINTER 2014
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Gene signature may improve colon cancer treatment


By Melissa Marino
July 2010

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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 Gastroenterology, could also help personalize treatments for colon cancer by identifying patients most likely to benefit from chemotherapy.

Using a mouse colon cancer cell line, R. Daniel Beauchamp, M.D., chair of the Section of Surgical Sciences, and colleagues first 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., 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.

In a larger patient population, they found that patients with the “poor prognosis” signature – the expression pattern seen in highly invasive mouse cells – were five times more likely to have a cancer recurrence than those with a “good” prognosis signature.

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.”

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