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. 2021 Apr 1:8:633951.
doi: 10.3389/fmolb.2021.633951. eCollection 2021.

Identification of Epithelial-Mesenchymal Transition-Related lncRNAs that Associated With the Prognosis and Immune Microenvironment in Colorectal Cancer

Chuan Liu  1 , Chuan Hu  2 , Jianyi Li  2 , Liqing Jiang  1 , Chengliang Zhao  2
Affiliations

Identification of Epithelial-Mesenchymal Transition-Related lncRNAs that Associated With the Prognosis and Immune Microenvironment in Colorectal Cancer

Chuan Liu et al. Front Mol Biosci. .

Abstract

Background: The expression of long non-coding RNA (lncRNA) is associated with the epithelial-mesenchymal transition (EMT) in tumorigenicity, but the role of EMT-related lncRNA in colorectal cancer (CRC) remains unclear. Methods: The clinical data and gene expression profile of CRC patients were obtained from The Cancer Genome Atlas database. Differential expression analysis, Cox regression model, and Kaplan-Meier analysis were used to study the relationship between EMT-related lncRNAs and the prognosis of CRC. Functional analysis and unsupervised clustering analysis were performed to explore the influence of certain lncRNAs on CRC. Finally, Cytoscape was used to construct mRNA-lncRNA networks. Results: Two signatures incorporating six and ten EMT-related lncRNAs were constructed for predicting the overall survival (OS) and disease-free survival (DFS), respectively. Kaplan-Meier survival curves indicated that patients in the high-risk group had a poorer prognosis than those in the low-risk group. The results of the functional analysis suggested that the P53 and ECM-receptor pathways affect the prognosis of CRC, and AL591178.1 is a key prognostic EMT-related lncRNA, which is negatively related to immune cells, P53 pathway, and ECM-receptor pathway. Conclusion: Six OS-related and ten DFS-related EMT-related lncRNAs were correlated with the prognosis of CRC by potentially affecting the immune microenvironment, and AL591178.1 plays a key role as a prognostic factor.

Keywords: colorectal cancer; epithelial-mesenchymal transition; immune cells; lncRNA; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Difference analysis. (A) a heat map shows all differentially expressed EMT-related lncRNA between normal and CRC tissues; (B) a volcano map shows different high-and low-expressed EMT-related lncRNA in normal and CRC tissues.
FIGURE 2
FIGURE 2
Development of prognostic models for CRC. OS (A,C) and DFS (B,D) in the training set (A,B) and validation set (C,D).
FIGURE 3
FIGURE 3
The mRNA-lncRNA co-expression network based on the correlation analysis. (A) the final OS signature; (B) the final DFS signature.
FIGURE 4
FIGURE 4
EMT-related lncRNA clusters significantly associated with the immune microenvironment. (A) Consensus clustering analysis identification of two clusters; (B,C) Kaplan–Meier survival curve of OS (B) and DFS (C) between C1 and C2; (D) Heat map of the lncRNA ordered by cluster, with annotations associated with each cluster; (E,F) Immune score and stromal score between the two clusters; (G) Statistical differences in each type of immune cell between C1 and C2.
FIGURE 5
FIGURE 5
Kaplan–Meier survival curve of OS (A–C) and DFS (D–F) based on the expression of MMP25-AS1 (A,D), AL591178.1 (B,E), and LINC01503 (C,F).
FIGURE 6
FIGURE 6
The relationship of EMT-related lncRNAs and pathways. (A,B) MMP25AS1 with the P53 pathway and the ECM receptor pathway; (C,D) AL591178.1 with the P53 pathway and the ECM receptor pathway; (E,F) LINC01503 with the P53 pathway and the ECM receptor pathway.
FIGURE 7
FIGURE 7
Association between 22 types of immune cells and the expression of AL591178.1.
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