Abstract
Background. Renal cell carcinoma (RCC) is asymptomatic up to severe stages and is characterized by a high mortality rate, reaching 90 % with the development of a metastatic process. Objective : to determine the group of microRNA genes, the methylation of which is associated with the progression of the disease, in particular, with metastasis. Materials and methods . Methylation-specific polymerase chain reaction in a representative sample of RCC patients (98 cases) showed an increase in the methylation status of 6 microRNA genes (MIR9-1, MIR9-3, MIR34b/c, MIR130b, MIR1258, MIR107) in tumor DNA samples relative to matched samples of histologically unchanged tissue. Results. For 4 genes (MIR9-1, MIR107, MIR130b, MIR1258), a significant association of methylation with late (III-IV) stages, tumor size, loss of differentiation, and metastasis to lymph nodes or distant organs was shown. These 4 genes were used to compose a potential metastatic prognosis marker system with a clinical sensitivity of 68 % and a specificity of 84 % (area under curve 0.83), which will be applied in the final development of a system for personalized therapy of RCC patients. Conclusion. The association of methylation of the MIR1258 with RCC metastasis has been shown for the first time and is of independent interest as a new promising marker for the prognosis of metastatic relapses.
Highlights
Renal cell carcinoma (RCC) is asymptomatic up to severe stages and is characterized by a high mortality rate, reaching 90 % with the development of a metastatic process
Objective: to determine the group of microRNA genes, the methylation of which is associated with the progression of the disease, in particular, with metastasis
For 4 genes (MIR9-1, MIR107, MIR130b, MIR1258), a significant association of methylation with late (III–IV) stages, tumor size, loss of differentiation, and metastasis to lymph nodes or distant organs was shown. These 4 genes were used to compose a potential metastatic prognosis marker system with a clinical sensitivity of 68 % and a specificity of 84 %, which will be applied in the final development of a system for personalized therapy of RCC patients
Summary
Renal cell carcinoma (RCC) is asymptomatic up to severe stages and is characterized by a high mortality rate, reaching 90 % with the development of a metastatic process. Methylation-specific polymerase chain reaction in a representative sample of RCC patients (98 cases) showed an increase in the methylation status of 6 microRNA genes (MIR9-1, MIR9-3, MIR34b/c, MIR130b, MIR1258, MIR107) in tumor DNA samples relative to matched samples of histologically unchanged tissue. For 4 genes (MIR9-1, MIR107, MIR130b, MIR1258), a significant association of methylation with late (III–IV) stages, tumor size, loss of differentiation, and metastasis to lymph nodes or distant organs was shown. These 4 genes were used to compose a potential metastatic prognosis marker system with a clinical sensitivity of 68 % and a specificity of 84 % (area under curve 0.83), which will be applied in the final development of a system for personalized therapy of RCC patients
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