Please use this identifier to cite or link to this item:
doi:10.22028/D291-37740
Title: | MicroRNA-30a-5pme : a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples |
Author(s): | Outeiro-Pinho, Gonçalo Barros-Silva, Daniela Aznar, Elena Sousa, Ana-Isabel Vieira-Coimbra, Márcia Oliveira, Jorge Gonçalves, Céline S. Costa, Bruno M. Junker, Kerstin Henrique, Rui Jerónimo, Carmen |
Language: | English |
Title: | Journal of Experimental & Clinical Cancer Research |
Volume: | 39 |
Issue: | 1 |
Publisher/Platform: | Springer Nature |
Year of Publication: | 2020 |
Free key words: | microRNA DNA methylation Clear cell renal cell carcinoma Biomarker Diagnosis Prognosis |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | Background The rising incidence of renal cell carcinomas (RCC) constitutes a significant challenge owing to risk of overtreatment. Because aberrant microRNA (miR) promoter methylation contributes to cancer development, we investigated whether altered miR-30a-5p expression associates with DNA promoter methylation and evaluated the usefulness as clear cell RCC (ccRCC) diagnostic and prognostic markers. Methods Genome-wide methylome and RNA sequencing data from a set of ccRCC and normal tissue samples from The Cancer Genome Atlas (TCGA) database were integrated to identify candidate CpG loci involved in cancer onset. MiR-30a-5p expression and promoter methylation were quantitatively assessed by PCR in a tissue set (Cohort #1) and urine sets (Cohorts #2 and 3) from IPOPorto and Homburg University Hospital. Non-parametric tests were used for comparing continuous variables. MiR-30a-5p promoter methylation (miR-30a-5pme) performance as diagnostic (receiver operator characteristics [ROC] - validity estimates) and prognostic [metastasis-free (MFS) and disease-specific survival (DSS)] biomarker was further validated in urine samples from ccRCC patients by Kaplan Meier curves (with log rank) and both univariable and multivariable analysis. Results Two significant hypermethylated CpG loci in TCGA ccRCC samples, correlating with miR-30a-5p transcriptional downregulation, were disclosed. MiR-30a-5pme in ccRCC tissues was confirmed in an independent patient’s cohort of IPOPorto and associated with shorter time to relapse. In urine samples, miR-30a-5pme levels identified cancer both in testing and validation cohorts, with 83% sensitivity/53% specificity and 63% sensitivity/67% specificity, respectively. Moreover, higher miR-30a-5pme levels independently predicted metastatic dissemination and survival. Conclusion To the best of our knowledge, this is the first study validating the diagnostic and prognostic potential of miR-30a-5pme for ccRCC in urine samples, providing new insights for its clinical usefulness as non-invasive cancer biomarker. |
DOI of the first publication: | 10.1186/s13046-020-01600-3 |
URL of the first publication: | https://jeccr.biomedcentral.com/articles/10.1186/s13046-020-01600-3 |
Link to this record: | urn:nbn:de:bsz:291--ds-377409 hdl:20.500.11880/34129 http://dx.doi.org/10.22028/D291-37740 |
ISSN: | 1756-9966 |
Date of registration: | 27-Oct-2022 |
Description of the related object: | Supplementary information |
Related object: | https://static-content.springer.com/esm/art%3A10.1186%2Fs13046-020-01600-3/MediaObjects/13046_2020_1600_MOESM1_ESM.tif https://static-content.springer.com/esm/art%3A10.1186%2Fs13046-020-01600-3/MediaObjects/13046_2020_1600_MOESM2_ESM.tif https://static-content.springer.com/esm/art%3A10.1186%2Fs13046-020-01600-3/MediaObjects/13046_2020_1600_MOESM3_ESM.tif https://static-content.springer.com/esm/art%3A10.1186%2Fs13046-020-01600-3/MediaObjects/13046_2020_1600_MOESM4_ESM.docx |
Faculty: | M - Medizinische Fakultät |
Department: | M - Urologie und Kinderurologie |
Professorship: | M - Prof. Dr. Michael Stöckle |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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s13046-020-01600-3.pdf | 1,96 MB | Adobe PDF | View/Open |
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