Navigation Links
Gene signature may improve colon cancer treatment

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 medicinein identifying subgroups of patients that will benefit from one treatment versus another treatment modality, trying to target those patients that are most likely to benefitand 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."


Contact: Melissa Marino
Vanderbilt University Medical Center

Related biology news :

1. CIC Teams with Docubase Systems to Deliver eSignature Enabled Document Management Solutions
2. CIC Teams with Docubase Systems to Deliver eSignature Enabled Document Management Solutions
3. Top-Three US Bank Chooses CIC Electronic Signature Technology for Branch-Wide Deployment
4. Reportlinker Adds World Dynamic Signature Verification Market Report
5. Parascript Technology Wins Online Signature Verification Competition
6. Parascript Signature Verification Technology Used by Moscow Law Firm to Detect Signature Fraud in $160,000 Debt Collection Case
7. Parascript Signature Verification Technology Used by Moscow Law Firm to Detect Signature Fraud in $160,000 Debt Collection Case
8. Striata and CIC Launch Integrated eSignature, eDelivery, and eBilling for the Financial Services Industry
9. Striata and CIC Launch Integrated eSignature, eDelivery, and eBilling for the Financial Services Industry
10. 2009 Signature Genomic Laboratories Travel Award winner announced
11. CHIs 5th Biomarker World Congress: Signature Event with Cutting-Edge Agenda
Post Your Comments:
(Date:11/11/2015)...   MedNet Solutions , an innovative SaaS-based eClinical technology ... pleased to announce that it will be a Sponsor of ... to be held November 17-19 in Hamburg ... of iMedNet , MedNet,s easy-to-use, proven and ... has been able to deliver time and cost savings of ...
(Date:11/10/2015)... YORK , Nov. 10, 2015 ... to behavioral biometrics that helps to identify and ... fraud. Signature is considered as the secure and ... the identification of a particular individual because each ... more accurate results especially when dynamic signature of ...
(Date:11/9/2015)... 9, 2015  Synaptics Inc. (NASDAQ: SYNA ), ... broader entry into the automotive market with a comprehensive ... pace of consumer electronics human interface innovation. Synaptics, industry-leading ... for the automotive industry and will be implemented in ... Europe , Japan , and ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today announced ... 29, 2015 at 11:00 a.m. Israel time, at ... 98 Yigal Allon Street, 36 th Floor, Tel Aviv, ... Eric Paneth and Izhak Tamir to the Board of ... as external directors; , approval of an amendment to certain terms ...
(Date:11/24/2015)... Nov. 24, 2015  Twist Bioscience, a company ... Leproust, Ph.D., Twist Bioscience chief executive officer, will ... on December 1, 2015 at 3:10 p.m. Eastern ... City. --> --> ... Twist Bioscience is on Twitter. Sign up to ...
(Date:11/24/2015)... , ... November 24, 2015 , ... InSphero AG, the ... cell culture models, has promoted Melanie Aregger to serve as Chief Operating Officer. ... served on the management team and was promoted to Head of InSphero ...
(Date:11/24/2015)... QC , Nov. 24, 2015 /CNW Telbec/ - ProMetic ... "Corporation") announced today that Mr. Pierre Laurin , President ... corporate presentation at the upcoming Piper Jaffray 27 th ... Palace Hotel, on December 1-2, 2015. st ... available for one-on-one meetings throughout the day. The presentation will ...
Breaking Biology Technology: