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Gene Profiles Might Help Guide Lung Cancer Care
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Page: << Prev | 1 | 2 | 3 | Next >> The consortium first compiled 442 lung adenocarcinoma samples from six institutions and then divided them into four test sets. For each sample, they collected gene expression data on some 22,000 genes found in these cancer samples. They also looked over clinical information, such as the stage of the cancer and the patients' outcomes.
Consortium members then used two of the test sets, including outcome data, to develop prognostic "classifiers" -- collections of genes whose changes in activity (expressing or producing proteins, for example), whether up or down, predict patient outcome.
Then, the researchers applied these classifiers -- eight were developed overall -- to the remaining two test sets in a so-called validation step. Unlike during the initial "training phase" of the study, patient outcome data at this stage was "blinded." That meant that the researchers had to let their gene signatures (with and without the aid of clinical data) predict patient outcome. Those predictions were then checked against the actual clinical data to measure their accuracy.
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The results, said Beer, were mixed.
"We found some [classifiers] work well on one test set but not both, and very few worked well on both, and some of the published signatures did not work very well at all," he said.
Performance was better for tumors of all disease stages than when focusing exclusively on stage 1 disease, he noted. But, in most cases, the addition of clinical data substantially improved the predictions.
For Beer, the data highlight the difficulties of working with such a variable disease as lung cancer, which stems from both genetic and environmental (i.e., smoking) factors.
"It would be wonderful if this was very easy, and you could do it very accurately, but in reality it doesn't work as well as hoped, and we are trying to understand why that is the case," he said. "Why does it work well in some patients but not in others? How do you improve it? How do we identify genes that are prognostic for everybody, or at least for specific subgroups of patients?"
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Copyright © 2008 ScoutNews, LLC. All rights reserved.
Last updated 7/21/2008
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SOURCES: David Beer, Ph.D., professor, department of thoracic surgery, Cancer Center, University of Michigan, Ann Arbor; Edward Kim, M.D., assistant professor, medicine, department of thoracic/head and neck oncology, University of Texas M.D. Anderson Cancer Center, Houston; Arul M. Chinnaiyan, M.D., Ph.D., director, Michigan Center for Translational Pathology, investigator, Howard Hughes Medical Institute, and S.P. Hicks Endowed Professor of Pathology, University of Michigan Medical School, Ann Arbor; July 20, 2008, Nature Medicine, online
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