MicroRNA Expression Characterizes Oligometastasis(es)
Open Access
- 13 December 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (12), e28650
- https://doi.org/10.1371/journal.pone.0028650
Abstract
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. Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy. 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. 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.Keywords
This publication has 54 references indexed in Scilit:
- Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonizationNature Medicine, 2011
- An autocrine TGF-β/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transitionMolecular Biology of the Cell, 2011
- Distant metastasis occurs late during the genetic evolution of pancreatic cancerNature, 2010
- The patterns and dynamics of genomic instability in metastatic pancreatic cancerNature, 2010
- Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: Evidence supporting a mesothelial-to-epithelial transitionGynecologic Oncology, 2010
- Ubiquitin Ligase Nedd4L Targets Activated Smad2/3 to Limit TGF-β SignalingMolecular Cell, 2009
- Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancerNature Medicine, 2009
- The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2Online Journal of Public Health Informatics, 2008
- Endogenous human microRNAs that suppress breast cancer metastasisNature, 2008
- Genetic heterogeneity of single disseminated tumour cells in minimal residual cancerThe Lancet, 2002