Identification of Differentially Expressed and Prognostic lncRNAs for the Construction of ceRNA Networks in Lung Adenocarcinoma.

Yimeng Cui,Weina Fan,Li Cai,Ningzhi Zhang,Shuai Zhang,Xin Wang,Ying Xing,Lulu Bi,Fanglin Tian,Yaowen Cui,Ruixue Gu,Yuechao Liu,Yuning Zhan,Zhiqian Zhang

doi:10.1155/2021/2659550

Yimeng Cui, Weina Fan + Show 12 more

Open Access

https://doi.org/10.1155/2021/2659550

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Abstract

Background Long noncoding RNAs (lncRNAs) could function as competitive endogenous RNAs (ceRNAs) to competitively adsorb microRNAs (miRNAs), thereby regulating the expression of their target protein-coding mRNAs. In this study, we aim to identify more effective diagnostic and prognostic markers for lung adenocarcinoma (LUAD). Methods We obtained differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) for LUAD by using The Cancer Genomes Atlas (TCGA) portal. Weighted gene coexpression network analysis (WGCNA) was performed to unveil core gene modules associated with LUAD. The Cox proportional hazards model was performed to determine the prognostic significance of DElncRNAs. The diagnostic and prognostic significance of DElncRNAs was further verified based on the receiver operating characteristic curve (ROC). Cytoscape was used to construct the ceRNA networks comprising the lncRNAs-miRNAs-mRNAs axis based on the correlation obtained from the miRcode, miRDB, and TargetScan. Results Compared with normal lung tissues, 2355 DElncRNAs, 820 DEmiRNAs, and 17289 DEmRNAs were identified in LUAD tissues. We generated 8 WGCNA core modules in the lncRNAs coexpression network, 5 modules in the miRNAs, and 12 modules in the mRNAs coexpression network, respectively. One lncRNA module (blue) consisting of 441 lncRNAs, two miRNA modules (blue and turquoise) containing 563 miRNAs, and one mRNA module (turquoise), which consisted of 15162 mRNAs, were mostly significantly related to LUAD status. Furthermore, 67 DEmRNAs were found to be tumor-associated as well as the target genes of the DElncRNAs-DEmiRNAs axis. Survival analyses showed that 6 lncRNAs (LINC01447, WWC2-AS2, OGFRP1, LINC00942, LINC01168, and AC005863.1) were significantly correlated with the prognosis of LUAD patients. Ultimately, the potential ceRNA networks including 6 DElncRNAs, 4 DEmiRNAs, and 22 DEmRNAs were constructed. Conclusion Our study indicated that 6 DElncRNAs had the possibilities as diagnostic and prognostic biomarkers for LUAD. The lncRNA-mediated ceRNA networks might provide novel insights into the molecular mechanisms of LUAD progression.

Highlights

Lung cancer is the leading cause of cancer-related death worldwide, of which lung adenocarcinoma (LUAD) is the dominant histological subtype, accounting for 40% of all cases [1, 2]
Volcano plots presented that 109 Long noncoding RNAs (lncRNAs) were downregulated, 48 miRNAs and 536 mRNAs were downregulated, and 532 lncRNAs, 176 miRNAs, and 4464 mRNAs were upregulated in LUAD samples (Figures 2(a)–2(c))
Due to the unfavorable prognosis and high mortality rate of LUAD, it is necessary to improve the strategy of diagnosis and treatment. e lncRNA-mediated competitive endogenous RNAs (ceRNAs) hypothesis proposed that lncRNA functions as a ceRNA to regulate the gene expression by influencing miRNA activity

Summary

Introduction

Lung cancer is the leading cause of cancer-related death worldwide, of which lung adenocarcinoma (LUAD) is the dominant histological subtype, accounting for 40% of all cases [1, 2]. Long noncoding RNAs (lncRNAs) could function as competitive endogenous RNAs (ceRNAs) to competitively adsorb microRNAs (miRNAs), thereby regulating the expression of their target protein-coding mRNAs. In this study, we aim to identify more effective diagnostic and prognostic markers for lung adenocarcinoma (LUAD). We obtained differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) for LUAD by using e Cancer Genomes Atlas (TCGA) portal. Cytoscape was used to construct the ceRNA networks comprising the lncRNAs-miRNAs-mRNAs axis based on the correlation obtained from the miRcode, miRDB, and TargetScan. We generated 8 WGCNA core modules in the lncRNAs coexpression network, 5 modules in the miRNAs, and 12 modules in the mRNAs coexpression network, respectively. 67 DEmRNAs were found to be tumor-associated as well as the target genes of the DElncRNAs-DEmiRNAs axis. The potential ceRNA networks including 6 DElncRNAs, 4 DEmiRNAs, and 22 DEmRNAs were constructed. Our study indicated that 6 DElncRNAs had the possibilities as diagnostic and prognostic biomarkers for LUAD. e lncRNA-mediated ceRNA networks might provide novel insights into the molecular mechanisms of LUAD progression

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