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. 2018 Dec 10:6:e6091.
doi: 10.7717/peerj.6091. eCollection 2018.

Screening of prognostic biomarkers for endometrial carcinoma based on a ceRNA network

Ming-Jun Zheng  1   2 , Rui Gou  1   2 , Wen-Chao Zhang  1   2 , Xin Nie  1   2 , Jing Wang  1   2 , Ling-Ling Gao  1   2 , Juan-Juan Liu  1   2 , Xiao Li  1   2 , Bei Lin  1   2
Affiliations

Screening of prognostic biomarkers for endometrial carcinoma based on a ceRNA network

Ming-Jun Zheng et al. PeerJ. .

Abstract

Objective: This study aims to reveal the regulation network of lncRNAs-miRNAs-mRNA in endometrial carcinoma (EC), to investigate the underlying mechanisms of EC occurrence and progression, to screen prognostic biomarkers.

Methods: RNA-seq and miRNA-seq data of endometrial carcinoma were downloaded from the TCGA database. Edge.R package was used to screen differentially expressed genes. A database was searched to determine differentially expressed lncRNA-miRNA and miRNA-mRNA pairs, to construct the topological network of ceRNA, and to elucidate the key RNAs that are for a prognosis of survival.

Results: We screened out 2632 mRNAs, 1178 lncRNAs and 189 miRNAs that were differentially expressed. The constructed ceRNA network included 97 lncRNAs, 20 miRNAs and 73 mRNAs. Analyzing network genes for associations with prognosies revealed 169 prognosis-associated RNAs, including 92 lncRNAs, 16miRNAs and 61 mRNAs.

Conclusion: Our results reveal new potential mechanisms underlying the carcinogenesis and progression of endometrial carcinoma.

Keywords: Endometrial carcinoma; Prognostic biomarker; ceRNA network.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Heatmap and volcano plots of differentially expressed RNAs.
(A) Heatmap plots of differentially expressed mRNAs. (B) Heatmap plots of differentially expressed lncRNAs. (C) Heatmap plots of differentially expressed miRNAs. The horizontal axis represents samples. Sample clusters are presented above the horizontal axis. The vertical axis represents RNAs. Red denotes upregulated genes, and green denotes downregulated genes. (D) Volcano plots of differentially expressed mRNAs. (E) Volcano plots of differentially expressed lncRNAs. (F) Volcano plots of differentially expressed miRNAs. The Y-axis denotes the log of FC (base 2) and the X-axis plots the negative log of the false discovery rate (FDR; base 10). Each point represents a gene. Green dots represent downregulated RNAs, red dots represent upregulated RNAs, and black dots represent non-DEGs.
Figure 2
Figure 2. Sankey diagram for the ceRNA network in EC and topology, and stability analysis.
(A) Each rectangle represents a gene, and the connection degree of each gene is displayed based on the size of the rectangle. (B) Node degree distribution analysis. (C) Closeness centrality distribution. (D) Shortest path distribution. (E) Node degree distribution density.
Figure 3
Figure 3. Regression analysis between the expression levels of DElncRNAs and DEmRNAs targeted by hsa-mir-195.
(A) Regression analysis between the expression levels of C2orf48 and PSAT1. (B) Regression analysis between the expression levels of C2orf48 and KIF23. (C) Regression analysis between the expression levels of C2orf48 andCEP55. (D) Regression analysis between the expression levels of C2orf48 and CDC25A. (E) Regression analysis between the expression levels of C2orf48 and CCNE1. (F) Regression analysis between the expression levels of C2orf48 and CBX2. The horizontal axis indicates mRNA expression, and the vertical axis indicates lncRNA expression. (Pearson’s r, correlation coefficient.) The upper and right edges are histograms of gene expression.
Figure 4
Figure 4. Biological function and pathway enrichment analysis of 73 DEmRNAs.
(A) Chord diagram showing the top 10 enriched GO clusters for 73 DEmRNAs. In each chord diagram, enriched GO clusters are shown on the right and genes contributing to enrichment are shown on the left. Upregulated DEmRNAs are displayed in red and downregulated DEmRNAs are displayed in blue. Each GO term is represented by one colored line. (B) Significant pathway enrichment of DEmRNAs. Diamonds represent the signaling pathways and ellipses represents the regulated genes.
Figure 5
Figure 5. Kaplan-Meier survival curves for the top four lncRNAs, miRNAs and mRNAs related to overall survival and expression validation.
(A–D) Kaplan-Meier survival curves for the top four lncRNAs. (E–H) Kaplan-Meier survival curves for the top four miRNAs. (I–L) Kaplan-Meier survival curves for the top four mRNAs. (M–P) Expression validation of the top four DEmRNAs correlated with survival. (Q–T) Expression validation of the top four DEmiRNAs correlated with survival.
Figure 6
Figure 6. Correlation between gene expression and clinicopathological parameters.
(A–B) Correlations between PSAT1 gene expression levels and clinical stage and histological classification in the TCGA database. (C–D) Correlations between KIF23 gene expression levels and clinical stage and histological classification. (E–F) Correlations between CCNE1 gene expression levels and clinical stage and histological classification. (G–H) Correlations between MCM4 gene expression levels and clinical stage and histological classification. ***P-value < 0.01.
Figure 7
Figure 7. Validation of the top four DEmRNAs and DEmiRNAs correlated with survival.
(A) Violin plots of PSAT1mRNA expression levels in the GSE17025 validation dataset. (B) Violin plots of KIF23 mRNA expression levels in the GSE17025 validation dataset. (C) Violin plots of MCM4 mRNA expression levels in the GSE17025 validation dataset. (D) Violin plots of CCNE1 mRNA expression levels in the GSE17025 validation dataset. (E) Scatter plots of the has-mir-195 miRNA expression levels in the GSE35794 validation dataset. (F) Scatter plots of the has-mir-140 miRNA expression levels in the GSE35794 validation dataset. (G) Scatter plots of the hsa-mir-200a miRNA expression levels in the GSE35794 validation dataset. (H) Scatter plots of the hsa-mir-205 miRNA expression levels in the GSE35794 validation dataset.
Figure 8
Figure 8. Flow chart of construction and analysis of ceRNA network.
The flow chart of construction of lncRNAs-miRNAs-mRNA regulation network in endometrial carcinoma.
See this image and copyright information in PMC

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