Microrna expression characterizes Oligometastasis(es)

Yves A. Lussier, H. Rosie Xing, Joseph K. Salama, Nikolai N. Khodarev, Yong Huang, Qingbei Zhang, Sajid A. Khan, Xinan Yang, Michael D. Hasselle, Thomas E. Darga, Renuka Malik, Hanli Fan, Samantha Perakis, Matthew Filippo, Kimberly Corbin, Younghee Lee, Mitchell C. Posner, Steven J. Chmura, Samuel Hellman, Ralph R. Weichselbaum

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere28650
JournalPloS one
Volume6
Issue number12
DOIs
StatePublished - Dec 13 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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