Three Eyes Are Better Than One: Multidimensional Approach Provides More Complete Picture of Possible Predictive Biomarkers

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Researchers at the Western Connecticut Health Network Biomedical Research Institute use a multidisciplinary integrated approach to discover possible predictive biomarkers of tumor behavior for people with colon cancer.

With our method, we combine information from genes, microRNA, and proteins to get a much better pattern of the biology of our patients. - Dr. Shiquan He, Biostatistician, WCHN Biomedical Research Institute

The goal of finding effective treatments for people with colorectal cancer based on their unique molecular characteristics is still elusive. Researchers from the Western Connecticut Health Network Biomedical Research Institute have harnessed the power of a multidimensional integrated approach to discover accurate predictors of tumor behavior by collectively examining microRNA, gene, and protein expression.

“Normally, studies look at one gene, one protein or one microRNA, but these methods are not effective enough to make accurate predictions that are clinically useful,” said Shiquan He, Biostatistician at the Western Connecticut Health Network Biomedical Research Institute. “With our method, we combine information from different dimensions – genes, microRNA, and proteins – to get a much better pattern of the biology of our patients.”

Dr. He and colleagues, Marisa Mariani, PhD and the Abraham and Mildred Goldstein Research Scholar, Dr. Cristiano Ferlini-the Rudy and Sally Ruggles Chief of Cancer Research, et al, analyzed a cohort of 267 patients with colorectal cancer to find possible predictors of outcome. Tumor samples were collected when the patients underwent their first surgery and before receiving any treatment. The patients then underwent treatment and were followed for outcomes. The results of the study were published in PLOS ONE.

The researchers used a multidimensional platform that combined nanofluidic technology with quantitative fluorescent immunohistochemistry to try to discover biomarkers that had a predictive accuracy of 80 percent to 90 percent.

At first, Dr. He and colleagues conducted separate analyses of microRNA, genes, and proteins in the tumor samples. Within each group, several markers of outcomes were discovered. The researchers then divided the patients according to those who survived less than 3 years (aggressive disease) and those who survived longer than 3 years (non-aggressive disease). All factors identified as predictive of outcomes, whether it was a gene, microRNA, or a protein, were then tested to see if they were a predictor of aggressiveness. Unfortunately, analyses showed that none of the factors identified had a high predictive accuracy, meaning that clinical decisions could not be made based on the information.

Therefore, an analysis was performed that would combine the information from all three of the dimensions examined. When this multidimensional analysis was performed, the biomarkers were found to have an accuracy approaching 90 percent.

“Although this may take some time to translate into something that is clinically useful, this biomarker discovery platform can give us additional clues as to where we should focus our attention,” said Dr. He.

The use of this multidimensional platform to discover biomarkers is just one of the recent discoveries coming out of Western Connecticut Health Network Biomedical Research Institute. Despite its small size, the organization has combined motivated physician researchers and generous philanthropists to create a cutting edge research facility that is focused on translational research.

Moving forward, Dr. He and colleagues want to explore other methods of combining biomarkers in the hope of one day discovering biomarkers with a predictive accuracy of 95 to 96 percent.

For more information about the Danbury Hospital Biomedical Research Institute, visit

About the “New” Western Connecticut Health Network
Western Connecticut Health Network is the region’s premier, patient-centered health care organization serving residents of Western Connecticut and adjacent New York. The organization is now anchored by three nationally recognized hospitals, Danbury Hospital, New Milford Hospital, and Norwalk Hospital, as well as their affiliated organizations. In addition to the three hospitals, the continuum of care offered includes numerous medical practices and sub-specialties across the region, home health care services, a nationally renowned biomedical research institute, the Western Connecticut Health Network Foundation, Norwalk Hospital Foundation, and other affiliates.

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Diane Burke
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