Dataset Information

MiR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma.

ABSTRACT: Biomarkers to guide the clinical treatment of patients with renal cell carcinoma (RCC) are not yet routinely available. MicroRNAs (miRNAs) have been demonstrated to serve as biomarkers for a number of types of cancer. Based on a previous study by this group, we hypothesize that several highly differentially expressed miRNAs may serve as tissue and plasma biomarkers in patients with RCC. The expression levels of miR-210, miR-224 and miR-141 were analyzed in tissue samples from the same cohort of 78 patients with RCC, in paired pre- and post-operative plasma samples from 66 patients with clear cell RCC (ccRCC) and in 67 healthy controls by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic (ROC) was used to evaluate the diagnostic accuracy associated with the expression of miR-210, miR-224 and miR-141. ROC curves revealed that the diagnostic accuracy (area under the curve) of tissue miR-210, miR-224, the ratio of miR-210/miR-141 (miR210/141), miR-224/miR-141 (miR224/141) and miR-210× miR-224/miR-141 (miR210×224/141) in ccRCC was 0.8329, 0.8511, 0.9412, 0.9898 and 0.9771, respectively. Notably, miR224/141 demonstrated the highest accuracy among these miRNAs for discriminating ccRCC tissues from normal tissues, with a sensitivity of 97.06% and a specificity of 98.53%. The expression levels of plasma miR-210 and miR-224 were significantly increased in patients compared with healthy control patients, and were reduced postoperatively (P<0.05). The diagnostic accuracy of plasma miR-210 and miR-224 were 0.6775 (89.55% sensitivity and 48.48% specificity) and 0.6056 (88.06% sensitivity and 40.91% specificity), respectively. The present study indicated that the tissue miR-224/miR-141 ratio is a potentially powerful tool for detecting ccRCC. However, plasma miR-210 and miR-224 may not be associated with diagnosis of ccRCC.

SUBMITTER: Chen X

PROVIDER: S-EPMC6036413 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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miR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma.

Chen Xuanyu X Lou Ning N Ruan Anming A Qiu Bin B Yan Yun Y Wang Xuegang X Du Quansheng Q Ruan Hailong H Han Weiwei W Wei Haibin H Yang Hongmei H Zhang Xiaoping X

Oncology letters 20180601 2

Biomarkers to guide the clinical treatment of patients with renal cell carcinoma (RCC) are not yet routinely available. MicroRNAs (miRNAs) have been demonstrated to serve as biomarkers for a number of types of cancer. Based on a previous study by this group, we hypothesize that several highly differentially expressed miRNAs may serve as tissue and plasma biomarkers in patients with RCC. The expression levels of miR-210, miR-224 and miR-141 were analyzed in tissue samples from the same cohort of ...[more]

PMID: 30008851

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Project description:BACKGROUND:Due to the poor prognosis for advanced renal cell carcinoma (RCC), there is an urgent need for new therapeutic targets and for prognostic markers to identify high risk tumors. MicroRNAs (miRNAs) are frequently dysregulated in tumors, play a crucial role during carcinogenesis and therefore might be promising new biomarkers. In previous studies, we identified miR-141-3p and miR-145-5p to be downregulated in clear cell RCC (ccRCC). Our objective was to investigate the functional association of these miRNAs, focusing on the cooperative regulation of new specific targets and their role in ccRCC progression. METHODS:The effect of miR-141-3p and miR-145-5p on cell migration was examined by overexpression in 786-O cells. New targets of both miRNAs were identified by miRWalk, validated in 786-O and ACHN cells and additionally characterized in ccRCC tissue on mRNA and protein level. RESULTS:In functional analysis, a tumor suppressive effect of miR-141-3p and miR-145-5p by decreasing migration and invasion of RCC cells could be shown. Furthermore, co-overexpression of the miRNAs seemed to result in an increased inhibition of cell migration. Both miRNAs were recognized as post-transcriptional regulators of the targets EAPP, HS6ST2, LOX, TGFB2 and VRK2. Additionally, they showed a cooperative effect again as demonstrated by a significantly increased inhibition of HS6ST2 and LOX expression after simultaneous overexpression of both miRNAs. In ccRCC tissue, LOX mRNA expression was strongly increased compared to normal tissue, allowing also to distinguish between non-metastatic and already metastasized primary tumors. Finally, in subsequent tissue microarray analysis LOX protein expression showed a prognostic relevance for the overall survival of ccRCC patients. CONCLUSION:These results illustrate a jointly strengthening effect of the dysregulated miR-141-3p and miR-145-5p in various tumor associated processes. Focusing on the cooperative effect of miRNAs provides new opportunities for the development of therapeutic strategies and offers novel prognostic and diagnostic capabilities.

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Project description: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.

Dataset Information

MiR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma.

Publications

miR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma.

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