Dataset Information

Prognostic value of genome-wide DNA methylation patterns in noncoding miRNAs and lncRNAs in uveal melanomas.

ABSTRACT:

Background

Uveal melanomas are the most common primary intraocular malignant tumors in adults, associated with a high metastasis rate and a low 5-year survival rate. It is a clinic urgency and importance to identify prognostic factors for UVMs.

Results

55 aberrantly methylated sites of miRNAs and 47 aberrantly methylated sites of lncRNAs were observed between Alive < 2 years group and Alive > 2 years group of UVMs. Two prognostic classifiers were generated. For 13- miRNAs-CpG-classifier, the AUC were 0.958, 0.848 and 0.824 at 1 year, 2 years and 3 years, respectively. For 9- lncRNAs-CpG-classifier, the AUC were 0.943, 0.869 and 0.866 at 1 year, 2 years and 3 years, respectively.

Conclusion

The correlation between genome-wide DNA methylation patterns of miRNAs and lncRNAs and the overall survival in UVMs were identified in this study. This novel finding shed new light on developing biomarkers of prognosis for UVMs.

Methods

DNA methylation profiles of noncoding miRNAs and lncRNAs for UVMs were accessed from The Cancer Genome Atlas. Then the prognostic value was analyzed by least absolute shrinkage and selection operator method Cox regression and tested by Time-dependent Receiver Operating Characteristic curve.

SUBMITTER: Zheng Z

PROVIDER: S-EPMC6738428 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Prognostic value of genome-wide DNA methylation patterns in noncoding miRNAs and lncRNAs in uveal melanomas.

Zheng Zheng Z Xu Dan D Shi Keqing K Chen Minfeng M Lu Fan F

Aging 20190820 16

<h4>Background</h4>Uveal melanomas are the most common primary intraocular malignant tumors in adults, associated with a high metastasis rate and a low 5-year survival rate. It is a clinic urgency and importance to identify prognostic factors for UVMs.<h4>Results</h4>55 aberrantly methylated sites of miRNAs and 47 aberrantly methylated sites of lncRNAs were observed between Alive < 2 years group and Alive > 2 years group of UVMs. Two prognostic classifiers were generated. For 13- miRNAs-CpG-clas ...[more]

PMID: 31433788

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Project description:Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high‑risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high‑grade vs. low‑grade) and status (deceased vs. alive); differential analyses of miRNA expression among these groups were performed. A total of 20 deregulated miRNAs for each group were identified. In total 7 miRNAs were common between the groups. The majority of common miRNAs belonged to the miR‑506‑514 cluster, known to be involved in UM development. The prognostic value of the 20 selected miRNAs related to tumor stage was assessed. The deregulation of 12 miRNAs (6 upregulated and 6 downregulated) was associated with a worse prognosis of patients with UM. Subsequently, miRCancerdb and microRNA Data Integration Portal bioinformatics tools were used to identify a set of genes associated with the 20 miRNAs and to establish their interaction levels. By this approach, 53 different negatively and positively associated genes were identified. Finally, DIANA‑mirPath prediction pathway and Gene Ontology enrichment analyses were performed on the lists of genes previously generated to establish their functional involvement in biological processes and molecular pathways. All the miRNAs and genes were involved in molecular pathways usually altered in cancer, including the mitogen‑activated protein kinase (MAPK) pathway. Overall, the findings of the presents study demonstrated that the miRNAs of the miR‑506‑514 cluster, hsa‑miR‑592 and hsa‑miR‑199a‑5p were the most deregulated miRNAs in patients with high‑grade disease compared to those with low‑grade disease and were strictly related to the overall survival (OS) of the patients. However, further in vitro and translational approaches are required to validate these preliminary findings.

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal carcinoma. Protein coding genes and non-coding RNAs can be powerful prognostic factors in multiple cancers, including ESCC. However, there is currently no model that integrates multiple types of RNA expression signatures to predict clinical outcomes.MethodsThe sequencing data (RNA-sequencing and miRNA-sequencing) and clinical data of ESCC patients were obtained from The Cancer Genome Atlas (TCGA) database, and Differential gene expression analysis, Cox regression analysis and Spearman correlation analysis were used to construct prognosis-related lncRNA-mRNA co-expression network and scoring system with multiple types of RNA. The potential molecular mechanisms of prognostic mRNAs were explored by functional enrichment analysis.ResultsA total of 62 prognostic lncRNAs, eight prognostic miRNAs and 66 prognostic mRNAs were identified in ESCC (P-value < 0.05) and a prognosis-related lncRNA-mRNA co-expression network was created. Five prognosis-related hub RNAs (CDCA2, MTBP, CENPE, PBK, AL033384.1) were identified. Biological process analysis revealed that mRNAs in prognosis-related co-expression RNA network were mainly enriched in cell cycle, mitotic cell cycle and nuclear division. Additionally, we constructed a prognostic scoring system for ESCC using ten signature RNAs (MLIP, TNFSF10, SIK2, LINC01068, LINC00601, TTTY14, AC084262.1, LINC01415, miR-5699-3p, miR-552-5p). Using this system, patients in the low-risk group had better long-term survival than those in the high-risk group (log-rank, P-value < 0.0001). The area under the ROC curve (AUCs) revealed that the accuracy of the prediction model was higher than the accuracy of single type of RNA prediction model.ConclusionIn brief, we constructed a prognostic scoring system based on multiple types of RNA for ESCC that showed high predicting prognosis performance, and deeply understood the regulatory mechanism of prognosis-related lncRNA-mRNA co-expression network.

Dataset Information

Prognostic value of genome-wide DNA methylation patterns in noncoding miRNAs and lncRNAs in uveal melanomas.

Background

Results

Conclusion

Methods

Publications

Prognostic value of genome-wide DNA methylation patterns in noncoding miRNAs and lncRNAs in uveal melanomas.

Similar Datasets

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