miR-155 and miR-484 Are Associated with Time to Progression in Metastatic Renal Cell Carcinoma Treated with Sunitinib
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26064968
PubMed Central
PMC4433647
DOI
10.1155/2015/941980
Knihovny.cz E-resources
- MeSH
- Adult MeSH
- Indoles administration & dosage MeSH
- Kaplan-Meier Estimate MeSH
- Carcinoma, Renal Cell drug therapy genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- MicroRNAs biosynthesis genetics MeSH
- Biomarkers, Tumor biosynthesis genetics MeSH
- Neovascularization, Pathologic drug therapy genetics pathology MeSH
- Disease Progression MeSH
- Pyrroles administration & dosage MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sunitinib MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Indoles MeSH
- MicroRNAs MeSH
- MIRN155 microRNA, human MeSH Browser
- MIRN484 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
- Pyrroles MeSH
- Sunitinib MeSH
Background. Sunitinib is a tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma. The main difficulty related to the treatment is the development of drug resistance followed by rapid progression of the disease. We analyzed tumor tissue of sunitinib treated patients in order to find miRNAs associated with therapeutic response. Methods. A total of 79 patients with metastatic renal cell carcinoma were included in our study. miRNA profiling in tumor tissue samples was performed by TaqMan Low Density Arrays and a group of selected miRNAs (miR-155, miR-374-5p, miR-324-3p, miR-484, miR-302c, and miR-888) was further validated by qRT-PCR. Normalized data were subjected to ROC and Kaplan-Meier analysis. Results. We reported decreased tissue levels of miR-155 and miR-484 as significantly associated with increased time to progression (miR-155: median TTP 5.8 versus 12.8 months, miR-484: median TTP 5.8 versus 8.9 months). Conclusion. miR-155 and miR-484 are potentially connected with sunitinib resistance and failure of the therapy. miR-155 is a known oncogene with direct influence on neovascularization. Biological role of miR-484 has to be clarified. Stratification of patients based on miRNA analysis would allow more personalized approach in therapy of metastatic renal cell carcinoma.
Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic
Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute 656 53 Brno Czech Republic
Department of Pharmacology Faculty of Medicine Masaryk University 625 00 Brno Czech Republic
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