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Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-110061
  • Background Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. Methods ExpressionBackground Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. Methods Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). Results RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. Conclusions A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.show moreshow less

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Metadaten
Author: Daniel Vergho, Susanne Kneitz, Andreas Rosenwald, Charlotte Scherer, Martin Spahn, Maximilian Burger, Hubertus Riedmiller, Burkhard Kneitz
URN:urn:nbn:de:bvb:20-opus-110061
Document Type:Journal article
Faculties:Medizinische Fakultät / Urologische Klinik und Poliklinik
Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Year of Completion:2014
Source:In: BMC Cancer 14:25 (2014). doi:10.1186/1471-2407-14-25
DOI:https://doi.org/10.1186/1471-2407-14-25
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Biomarker; Kidney cancer; Profiling; Prognosis; RCC; Renal cell carcinoma; Tumour markers; miR-126; miR-21; miRNA
Release Date:2015/02/27
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2014
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung