Dataset Information

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma.

ABSTRACT: Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro.

SUBMITTER: Mlcochova H

PROVIDER: S-EPMC4994011 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma.

Mlcochova Hana H Machackova Tana T Rabien Anja A Radova Lenka L Fabian Pavel P Iliev Robert R Slaba Katerina K Poprach Alexandr A Kilic Ergin E Stanik Michal M Redova-Lojova Martina M Svoboda Marek M Dolezel Jan J Vyzula Rostislav R Jung Klaus K Slaby Ondrej O

Scientific reports 20160823

Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into d ...[more]

PMID: 27549611

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Project description:BackgroundAcute myeloid leukemia (AML) is a highly heterogenous disease with varying clinical outcomes among patients. Epithelial-mesenchymal transition (EMT) is an important mechanism underlying cancer metastasis and chemotherapy resistance. However, few EMT-based signatures have been established to predict AML prognosis and treatment efficacy.MethodsBy conducting comparative RNA-seq analysis, we discovered the differential expression of EMT genes between AML patients with relapse and those without relapse. Based on the prognostic analysis of the differentially expressed EMT genes, a metastasis-related EMT signature (MEMTs) was constructed. An analysis was conducted on both TARGET and TCGA cohorts to explore the possible association between MEMTs and prognosis in AML. Three separate chemotherapy treatment cohorts were utilized to assess the predictive efficacy of MEMTs for chemotherapy response. In addition, the potential correlation between MEMTs and the tumor microenvironment was also investigated. Finally, random forest analysis and functional experiments were conducted to verify the key MEMTs gene associated with AML metastasis.ResultsBased on expression and prognostic analysis, we constructed MEMTs that include three EMT genes (CDH2, LOX, and COL3A1). Our findings suggested that the MEMTs could act as a prognostic factor for AML patients, and furthermore, it proved to be a predictor of their response to chemotherapy. Specifically, high MEMTs was associated with worse prognosis and poor response to chemotherapy, while low MEMTs was linked to better prognosis and higher response rates. Random forest and functional experiments demonstrate that CDH2 is a key gene promoting leukemia cell metastasis among the three MEMTs genes.ConclusionThe identification of MEMTs could potentially act as a predictor for the prognosis and the response to chemotherapy in AML patients. Individual tumor evaluation based on MEMTs could provide personalized treatment options for AML patients in the future.

Project description:BackgroundA rising amount of data demonstrates that the epithelial-mesenchymal transition (EMT) in clear cell renal cell carcinomas (ccRCC) is connected with the advancement of the cancer. In order to understand the role of EMT in ccRCC, it is critical to integrate molecules involved in EMT into prognosis prediction. The objective of this project was to establish a prognosis prediction model using genes associated with EMT in ccRCC.MethodsWe acquired the mRNA expression profiles and clinical information about ccRCC from TCGA database. In this study, we measured differentially expressed EMT-related genes (DEEGs) by two comparison groups (tumor versus normal tissues; "stages I-II" versus "stages III-IV" tumor tissues). Based on classification and regression random forest models, we identified the most important DEEGs in predicting prognosis. Afterwards, a risk-score model was created using the identified important DEEGs. The prediction ability of the risk-score model was calculated by the area under the curve (AUC). A nomogram for prognosis prediction was built using the risk-score in combination with clinical factors.ResultsAmong the 72 DEEGs, the classification and regression random forest models identified six hub genes (DKK1, DLX4, IL6, KCNN4, RPL22L1, and SPDEF), which exhibited the highest importance values in both models. Through the expression of these six hub genes, a novel risk-score was developed for the prognosis prediction of ccRCC. ROC curves showed the risk-score performed well in both the training (0.749) and testing (0.777) datasets. According to the survival analysis, individuals who were separated into high/low-risk groups had statistically different outcomes in terms of prognosis. Besides, the risk-score model also showed outstanding ability in assessing the progression of ccRCC after treatment. In terms of nomogram, the concordance index (C-index) was 0.79. Additionally, we predicted the differences in response to chemotherapy drugs among patients from low- and high-risk groups.ConclusionGene signatures related to EMT could be useful in predicting ccRCC prognosis.

Dataset Information

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma.

Publications

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma.

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