Micro‐RNA profiles in osteosarcoma as a predictive tool for ifosfamide response
Open Access
- 14 October 2010
- journal article
- early detection-and-diagnosis
- Published by Wiley in International Journal of Cancer
- Vol. 129 (3), 680-690
- https://doi.org/10.1002/ijc.25715
Abstract
Micro‐RNAs (miRNA) are currently used as cancer biomarkers for hematological cancers and solid tumors. Osteosarcoma is the first primary malignant bone tumor, characterized by a complex genetic and resistance to conventional treatments. For this latter property, the median survival has not been improved since 1990 despite preoperative administration of chemotherapeutic agents. The prediction of tumor response before chemotherapy treatment would constitute a major progress for this pathology. We assessed in this study if miRNA profiling could surpass the current limitations for osteosarcoma diagnosis. We measured the miRNA expression in different osteosarcoma samples: (i) 27 osteosarcoma paraffin‐embedded tumors from patients, (ii) human osteosarcoma cell lines, and (iii) tumors from a syngeneic rat osteosarcoma model, recapitulating human osteosarcoma. miRNA profiles were determined using microfluidic cards performing high‐throughput TaqMan®‐based PCR assays, called TaqMan® Low Density Arrays. Osteosarcoma of rat and human origins showed a miRNA signature, which could discriminate good from bad responders. In particular, we identified five discriminating miRNAs (miR‐92a, miR‐99b, miR‐132, miR‐193a‐5p and miR‐422a) in patient tumors, which could be easily transferable to diagnosis. These discriminating miRNAs, as well as those identified in rat, targeted the TGFβ, the Wnt and the MAP kinase pathways. These results indicate that our platform constitutes a potent diagnostic tool to predict tumor sensitivity to a drug in attempt to better adapt treatment to tumor biological specificities and also to identify new potential therapeutic strategies.Keywords
This publication has 42 references indexed in Scilit:
- Biological Functions of miR-29b Contribute to Positive Regulation of Osteoblast DifferentiationPublished by Elsevier BV ,2009
- MicroRNA‐223 is a key factor in osteoclast differentiationJournal of Cellular Biochemistry, 2007
- A developmental view of microRNA functionTrends in Biochemical Sciences, 2007
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006
- A microRNA expression signature of human solid tumors defines cancer gene targetsProceedings of the National Academy of Sciences of the United States of America, 2006
- MicroRNA expression profiles classify human cancersNature, 2005
- MicroRNAs: small RNAs with a big role in gene regulationNature Reviews Genetics, 2004
- Specificity of microRNA target selection in translational repressionGenes & Development, 2004
- A microRNA in a Multiple-Turnover RNAi Enzyme ComplexScience, 2002
- MicroRNA maturation: stepwise processing and subcellular localizationThe EMBO Journal, 2002