Gene screen may lead to individualized treatment of patients with lung cancer
By Deborah Wormser
Researchers at UT Southwestern Medical Center have used an innovative computational and systems biology approach to identify a set of 12 genes that may predict which patients with the most common form of lung cancer are most likely to benefit from adjuvant chemotherapy (ACT) following surgery.
“This is the first study to integrate a computational approach with genome-wide data to identify a gene set that may be capable of predicting potential benefits arising from individualized treatments,” said Dr. Yang Xie, Associate Professor of Clinical Sciences.
Published in the March issue of Clinical Cancer Research, the study used several data sets – all established from early-stage non-small cell lung cancer (NSCLC) patients – that provided information from more than 1,350 cases. The researchers used various analytical tools to identify 18 potential candidate genes that were later narrowed to the 12-gene screening set. They also studied genetic alterations of early-stage NSCLC cells compared to noncancerous cells, and they worked to identify genes that associated with a better response to chemotherapy, explained Dr. Xie, the study’s senior author. The lead author is Dr. Hao Tang, Assistant Professor of Clinical Sciences.
Clinical trials have demonstrated a survival benefit from ACT after surgery, which is performed on about 85 percent of all lung cancer patients, according to the American Cancer Society. The response to standard chemotherapy, however, varies considerably, and thus it would be extremely helpful if doctors could identify which patients are most likely to benefit from ACT, Dr. Xie said.
The next step will be to develop a robust clinical assay based on these results, a project she is planning with fellow authors Drs. John Minna and Joan Schiller, and with researchers at the National Cancer Institute (NCI). Dr. Minna is Director of the W.A. “Tex” and Deborah Moncrief Jr. Center for Cancer Genetics and the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research. Dr. Schiller is Chief of Hematology-Oncology as well as Deputy Director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.
UT Southwestern has filed a patent application on the gene screen.
The study in Clinical Cancer Research was data-driven, meaning the investigators gathered enormous amounts of data and then used statistical and computational approaches to extract useful information from it, Dr. Xie said. Combining their approach with real patient data from the NCI Lung Cancer Specialized Programs of Research Excellence (SPORE) grant led by Dr. Minna helped speed the project.
A prospective study to collect data going forward is necessary to provide information that is unattainable in a retrospective study such as this one, Dr. Xie said. The long-term goal is to use translational research strategies to build on these initial bioinformatics findings to create a 12-gene screen that could be used clinically.
“We believe this work integrates computational and systems biology with lab (cell line) work and patient data and has the potential to impact lung cancer patients’ care,” Dr. Xie said.
She said this study builds on the work performed in the laboratory of Dr. Michael White, Professor of Cell Biology. In 2007, Dr. White and his colleagues wrote a seminal paper in Nature that identified genes that help chemotherapy drugs kill lung cancer cells. Dr. Schiller’s participation bridged the lab work with patient care.
The study was funded by the NCI, the National Science Foundation, NASA, the Department of Defense, the Welch Foundation, and the Cancer Prevention and Research Institute of Texas.
Other UT Southwestern researchers involved were Dr. Guanghua Xiao, Associate Professor of Clinical Sciences; and Jeffrey Allen, a computational biologist in Clinical Sciences. Investigators at UT M.D. Anderson Cancer Center and Lawrence Berkeley National Laboratory in California also contributed.
Dr. Minna holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research, and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology.
Dr. Schiller holds the Andrea L. Simmons Distinguished Chair in Cancer Research.
Dr. White holds the Sherry Wigley Crow Cancer Research Endowed Chair, in Honor of Robert Lewis Kirby, M.D., and the Grant A. Dove Chair for Research in Oncology.