Journal
PLOS ONE
Volume 6, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0028650
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Funding
- Ludwig Center for Metastasis Research
- Center for Radiation Therapy
- Chicago Tumor Institute
- Dr. Lloyd Old, Mr. and Mrs. Vincent Foglia and the Foglia foundation
- Lung Cancer Research Foundation
- Cancer Research Foundation
- NIH [K22 LM008308-04, 5UL1RR024999-04]
- University of Chicago Comprehensive Cancer Center [5P30CA014599-35]
- National Center for the Multi Scale Analysis of Genomic and Cellular Networks (MAGNeT) [5U54CA121852-5]
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Background: Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by <= 5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy. Methods: Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy. Results: Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression. Conclusions: These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.
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