Comprehensive Analysis of N6-Methyladenosine-Related lncRNA Signature for Predicting Prognosis and Immune Cell Infiltration in Patients with Colorectal Cancer.

Zhan Zhao,Hui Ding,Yi-Ran Zhang,Ya-Bing Yang,Zheng-Bin Lin,Liang Wang,Xiao-Dong Chu,Yun-Long Pan,Xin-Yuan Li,Xu-Guang Li,Jing-Hua Pan,Yan-Guan Guo

doi:10.1155/2021/8686307

Abstract

Background Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified. Methods We use “limma” R package, “glmnet” R package, and “survival” R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC. Result We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group (P < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs. Conclusion The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.

Highlights

Colorectal cancer (CRC) is the third most common malignancy worldwide and has become a leading cause of cancer-related death [1, 2]
We first summarized the incidence of copy number variations and somatic mutations of 24 m6A regulators in CRC
The results showed that the scores of DC, plasmacytoid dendritic cells, and mast cells in highrisk patients were lower than those of the low-risk group (Figure 8(a))

Summary

Introduction

Colorectal cancer (CRC) is the third most common malignancy worldwide and has become a leading cause of cancer-related death [1, 2]. Aberrant M6A modification promoted the progression of tumorigenesis in CRC by regulating the level of SOX2 transcripts, which can predict the poor prognosis in CRC [15]. The prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified. We comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC. We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients

Methods

Results

Conclusion