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. 2020 Jan 1;11(1):108-120.
doi: 10.7150/jca.35801. eCollection 2020.

Identification of a six-lncRNA signature based on a competing endogenous RNA network for predicting the risk of tumour recurrence in bladder cancer patients

Danfeng Zhao  1   2 , Qiang Peng  1 , Lu Wang  1   2 , Cong Li  1 , Yulin Lv  1   2 , Yong Liu  3 , Zhichao Wang  1 , Ruizhe Fang  1 , Jiaqi Wang  1   2 , Zhongqing Liu  1 , Wanhai Xu  1   2
Affiliations

Identification of a six-lncRNA signature based on a competing endogenous RNA network for predicting the risk of tumour recurrence in bladder cancer patients

Danfeng Zhao et al. J Cancer. .

Abstract

Bladder cancer (BC) is the most common malignancy involving the urinary system, and is characterized by a high recurrence rate. It is important to identify potential lncRNA signatures capable of predicting tumour recurrence risk and assessing recurrence prognosis in BC patients. We extracted data from The Cancer Genome Atlas and identified 381 differentially expressed lncRNAs, 855 mRNAs and 70 miRNAs between non-recurrent and recurrent BC tissues. Subsequently, a competing endogenous RNA (ceRNA) network composed of 29 lncRNAs, 13 miRNAs and 4 mRNAs was established. We used univariate and multivariate Cox regression to analyse the relationship between the 29 lncRNAs and recurrence-free survival (RFS) in BC patients. Six lncRNAs had significant prognostic values, and their cumulative risk score indicated that this 6-lncRNA signature independently predicted RFS in BC patients. We applied a receiver operating characteristic (ROC) analysis to assess the efficiency of our prognostic models. High-risk patients exhibited a poorer prognosis than low-risk patients did. Additionally, the 6-lncRNA signature showed a significant correlation with BC clinicopathological characteristics, which indicates that it could be used for effective risk stratification. The current study provides novel insights into the lncRNA-related ceRNA network and this 6-lncRNA signature may be an independent prognostic factor in predicting the recurrence of BC patients.

Keywords: Bladder cancer; LncRNA; Recurrence free survival; Recurrence risk; ceRNA network.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Differential expression of RNAs between non-recurrent and recurrent BC tissues. A, Volcano plots showing the differential expression of RNAs (mRNAs, lncRNAs, and miRNAs) and B, heatmaps demonstrate differential expression of RNAs (mRNAs, lncRNAs, and miRNAs).
Figure 2
Figure 2
Gene Ontology and KEGG pathways enrichment analysis of differentially expressed mRNAs. The 10 most significantly GO results covering domains of A, biological processes (BP), B, cellular component (CC) and C, molecular function (MF). D, The 10 most significantly enriched KEGG pathways.
Figure 3
Figure 3
The ceRNA network of lncRNA-miRNA-mRNA. In network the blue nodes indicate down-regulated expression, and the red nodes indicate up-regulated expression. Rectangles represent miRNAs, ellipses represent protein-coding genes, and diamonds represent lncRNAs; gray edges indicate lncRNA-miRNA-mRNA interactions.
Figure 4
Figure 4
Six-lncRNA signature predicted RFS in bladder cancer patients. Kaplan-Meier survival curves of RFS between high-risk and low-risk patients, the distributions of A, patients' risk score B, recurrence status and C, heat map of the six-lncRNA expression profiles in low- and high-risk patients.
Figure 5
Figure 5
ROC curves and Kaplan-Meier plot based on the integrated classifier in bladder cancer patients. A, Kaplan-Meier analysis of recurrence free survival between the high‑risk and low‑risk groups. B, Time-dependent ROC curve with AUC of risk score built by the 6-lncRNA signature. C, Kaplan-Meier analysis of recurrence free survival between stage I+II and stage III+IV patients D, Time-dependent ROC curve analysis of pathological stage.
Figure 6
Figure 6
Expression pattern of the 6-lncRNA (AC012640.1, STEAP3-AS1, NAV2-AS2, MEG8, GLIS3-AS1, and LINC00158). A-F, recurrence and non-recurrence bladder cancer tissues, and G-L, high- risk and low- risk groups.
Figure 7
Figure 7
Correlations between clinical parameters and prognostic six signature lncRNAs in bladder cancer. The numbers in each block indicate the P-value. The bluer the block, the smaller the P-value.
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