title: miR-155 and miR-484 Are Associated with Time to Progression in Metastatic Renal Cell Carcinoma Treated with Sunitinib.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Merhautova
authors.affiliation: 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.
authors.forename: Renata
authors.identifier: 0000-0001-5373-6474
authors.initials: R
authors.lastname: Hezova
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
authors.forename: Alexandr
authors.identifier: 0000-0003-4698-9195
authors.initials: A
authors.lastname: Poprach
authors.affiliation: Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Kovarikova
authors.affiliation: Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.affiliation: 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.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Regina
authors.initials: R
authors.lastname: Demlova
authors.affiliation: 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.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; C524942:MIRN155 microRNA, human; C572386:MIRN484 microRNA, human; D035683:MicroRNAs; D011758:Pyrroles; D000077210:Sunitinib