Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 11:2021:4093426.
doi: 10.1155/2021/4093426. eCollection 2021.

Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma

Lixian Chen  1 , Zhonglu Ren  2   3 , Yongming Cai  2   3
Affiliations

Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma

Lixian Chen et al. Biomed Res Int. .

Abstract

Increasing evidence has shown that noncoding RNAs play significant roles in the initiation, progression, and metastasis of tumours via participating in competing endogenous RNA (ceRNA) networks. However, the survival-associated ceRNA in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we aimed to investigate the regulatory mechanisms underlying ceRNA in LUAD to identify novel prognostic factors. mRNA, lncRNA, and miRNA sequencing data obtained from the GDC data portal were utilized to identify differentially expressed (DE) RNAs. Survival-related RNAs were recognized using univariate Kaplan-Meier survival analysis. We performed functional enrichment analysis of survival-related mRNAs using the clusterProfiler package of R and STRING. lncRNA-miRNA and miRNA-mRNA interactions were predicted based on miRcode, Starbase, and miRanda. Subsequently, the survival-associated ceRNA network was constructed for LUAD. Multivariate Cox regression analysis was used to identify prognostic factors. Finally, we acquired 15 DE miRNAs, 49 DE lncRNAs, and 843 DE mRNAs associated with significant overall survival. Functional enrichment analysis indicated that survival-related DE mRNAs were enriched in cell cycle. The survival-associated lncRNA-miRNA-mRNA ceRNA network was constructed using five miRNAs, 49 mRNAs, and 21 lncRNAs. Furthermore, seven hub RNAs (LINC01936, miR-20a-5p, miR-31-5p, TNS1, TGFBR2, SMAD7, and NEDD4L) were identified based on the ceRNA network. LINC01936 and miR-31-5p were found to be significant using the multifactorial Cox regression model. In conclusion, we successfully constructed a survival-related lncRNA-miRNA-mRNA ceRNA regulatory network in LUAD and identified seven hub RNAs, which provide novel insights into the regulatory molecular mechanisms associated with survival of LUAD, and identified two independent prognostic predictors for LUAD.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Flow chart of ceRNA network construction.
Figure 2
Figure 2
Volcano plots of the DE RNAs: (a) DE mRNAs, (b) DE lncRNAs, and (c) DE miRNAs. The green dots indicated downregulated DE RNAs and the red indicated upregulated DE RNAs in tumour samples. The black dots indicated excluded RNAs.
Figure 3
Figure 3
The first 10 GO terms of survival-related DE mRNAs in LUAD from clusterProfiler.
Figure 4
Figure 4
The first 10 terms of survival-related DE mRNAs from STRING.
Figure 5
Figure 5
The KEGG pathways of survival-related DE mRNAs in LUAD. The x-axis indicates the number of mRNAs participated in the pathway.
Figure 6
Figure 6
Survival-related lncRNA-miRNA-mRNA ceRNA network of LUAD. The diamonds represent lncRNAs, ellipse mRNAs, and square miRNAs. The red represents upregulated genes, and the blue represents downregulated genes. The shade of the colour represents the magnitude of the value.
Figure 7
Figure 7
The subnetwork of survival-related ceRNA network. The shade of the colour represents the magnitude of MCC score.
Figure 8
Figure 8
Correlation analysis between lncRNAs and mRNAs of subnetwork: (a) LINC01936 and TNS1, (b) LINC01936 and PREX1, (c) MIR99HG and TNS1, and (d) MIR99HG and PREX1.
Figure 9
Figure 9
Kaplan-Meier curves of 7 hub RNAs: (a) LINC01936, (b) miR-31-5p, (c) miR-20a-5p, (d) TNS1, (e) TGFBR2, (f) SMAD7, and (g) NEDD4L.
Figure 10
Figure 10
Protein-protein interaction network of survival-related mRNAs in ceRNA network. Size of node represents degree value of mRNA. Line thickness represents the strength of data support (combine score).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R. L., Torre L. A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2018;68(6):394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Zhang L., Li M., Wu N., Chen Y. Time trends in epidemiologic characteristics and imaging features of lung adenocarcinoma: a population study of 21,113 cases in China. PLoS One. 2015;10(8, article e0136727) doi: 10.1371/journal.pone.0136727. - DOI - PMC - PubMed
    1. Lin J. J., Cardarella S., Lydon C. A., et al. Five-Year Survival in _EGFR_ -Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. Journal of Thoracic Oncology. 2016;11(4):556–565. doi: 10.1016/j.jtho.2015.12.103. - DOI - PMC - PubMed
    1. Tsao M.-S., Sakurada A., Cutz J.-C., et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. New England Journal of Medicine. 2005;353(2):133–144. doi: 10.1056/NEJMoa050736. - DOI - PubMed
    1. Hanna N., Ohana P., Konikoff F., et al. Phase 1/2a, dose-escalation, safety, pharmacokinetic and preliminary efficacy study of intratumoral administration of BC-819 in patients with unresectable pancreatic cancer. Cancer Gene Therapy. 2012;19(6):374–381. doi: 10.1038/cgt.2012.10. - DOI - PubMed

MeSH terms

LinkOut - more resources