Gene Flux Can Foretell Survival For Trauma Patients, Princeton Study Finds

The onset of inflammation and infection in a person recovering from a trauma such as a car accident or severe burns can be as deadly as the incident itself. New findings from Princeton University researchers who studied gene activity in trauma victims may help to predict and better treat such unexpected complications. Princeton research reported in the Sept. 13 issue of the journal PLoS Medicine shows for the first time that people recovering from a serious injury -- regardless of age, gender or previous health -- exhibit similar gene activity as their condition changes, which doctors can use to predict and prepare for a patient's deterioration.

The Princeton researchers' evaluation of blood samples from 168 blunt-force trauma patients revealed that changes in gene activity -- or expression -- in the immune system consistently coincided with the worsening of a patient's condition. Immune system genes "express" via an outpouring of proteins to help activate and direct the cellular response to injury and viruses, bacteria or other pathogens. Two sets of genes in particular showed massive fluctuations in expression as patients developed complications and neared death.

After the researchers identified the genes that were most in step with a patient's state of health, they created a model based on gene expression that could help physicians better evaluate and treat critical patients.

"Plenty of genes were changing inside these patients as their bodies adjusted to the trauma they experienced, but we wanted to find the genes that, over time, foretold the outcome for the patient," said senior author John Storey, a Princeton associate professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics. He worked with the PLoS Medicine paper's joint first authors Keyur Desai and Chuen-Seng Tan, both postdoctoral research fellows in Storey's lab.

"We started this project three years ago with approximately 50,000 documented gene expressions in these patients," Storey said. "We were amazed to see that as the list of genes directly related to a patient's health became smaller, the biological picture became clearer and we could pinpoint specific pathways. It was startling to see something so clean emerge from a study with so many variables."

The $100-million search for the genomic response to trauma

The Princeton findings are the latest to stem from a 10-year, $100-million effort to unravel the genomic underpinnings of why people experience vastly different outcomes to similar traumatic injuries. Based at Massachusetts General Hospital, the Inflammation and the Host Response to Injury (IHRI) project brought together more than 60 researchers from various U.S. universities. The IHRI consortium studied 1,977 severely injured and burned patients at U.S. trauma centers from 2003 to 2011, and the Princeton researchers worked with data from 168 of those patients. The National Institute of General Medical Sciences, a division of the National Institutes of Health, funded the project through its Large Scale Collaborative Projects, or "Glue Grant," program.