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Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients

BACKGROUND: N6-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C) can modify long non-coding RNAs (lncRNAs), thereby affecting tumorigenesis and tumor progression. However, there is a lack of knowledge regarding the potential roles and cross-talk of m(6)A- and m(5)C-related lncRNAs in the tumor mi...

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Autores principales: Song, Wei, Ren, Jun, Xiang, Rensheng, Yuan, Wenzheng, Fu, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957790/
https://www.ncbi.nlm.nih.gov/pubmed/35350786
http://dx.doi.org/10.3389/fimmu.2022.740960
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author Song, Wei
Ren, Jun
Xiang, Rensheng
Yuan, Wenzheng
Fu, Tao
author_facet Song, Wei
Ren, Jun
Xiang, Rensheng
Yuan, Wenzheng
Fu, Tao
author_sort Song, Wei
collection PubMed
description BACKGROUND: N6-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C) can modify long non-coding RNAs (lncRNAs), thereby affecting tumorigenesis and tumor progression. However, there is a lack of knowledge regarding the potential roles and cross-talk of m(6)A- and m(5)C-related lncRNAs in the tumor microenvironment (TME) and their effect on prognosis. METHODS: We systematically evaluated the expression patterns of m(6)A- and m(5)C-related lncRNAs in 1358 colorectal cancer (CRC) samples from four datasets. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance, TME, tumor-infiltrating immune cells (TIICs), and immune checkpoints in the different molecular subtypes were analyzed. Finally, we established a m(6)A- and m(5)C-related lncRNA signature and a prognostic nomogram. RESULTS: We identified 141 m(6)A- and m(5)C-related lncRNAs by co-expression analysis, among which 23 lncRNAs were significantly associated with the overall survival (OS) of CRC patients. Two distinct molecular subtypes (cluster A and cluster B) were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, TIICs, immune checkpoints. Next, a m(6)A- and m(5)C-related lncRNA signature for predicting OS was constructed, and its predictive capability in CRC patients was validated. We then constructed a highly accurate nomogram for improving the clinical applicability of the signature. Analyses of clinicopathological features, prognosis, TIICs, cancer stem cell (CSC), and drug response revealed significant differences between two risk groups. In addition, we found that patients with a low-risk score exhibited enhanced response to anti-PD-1/L1 immunotherapy. Functional enrichment analysis showed that these lncRNAs related to the high-risk group were involved in the development and progression of CRC. CONCLUSIONS: We conducted a comprehensive analysis of m(6)A- and m(5)C-related lncRNAs in CRC and revealed their potential functions in predicting tumor-immune-stromal microenvironment, clinicopathological features, and prognosis, and determined their role in immunotherapy. These findings may improve our understanding of the cross-talk between m(6)A- and m(5)C-related lncRNAs in CRC and pave a new road for prognosis assessment and more effective immunotherapy strategies.
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spelling pubmed-89577902022-03-28 Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients Song, Wei Ren, Jun Xiang, Rensheng Yuan, Wenzheng Fu, Tao Front Immunol Immunology BACKGROUND: N6-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C) can modify long non-coding RNAs (lncRNAs), thereby affecting tumorigenesis and tumor progression. However, there is a lack of knowledge regarding the potential roles and cross-talk of m(6)A- and m(5)C-related lncRNAs in the tumor microenvironment (TME) and their effect on prognosis. METHODS: We systematically evaluated the expression patterns of m(6)A- and m(5)C-related lncRNAs in 1358 colorectal cancer (CRC) samples from four datasets. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance, TME, tumor-infiltrating immune cells (TIICs), and immune checkpoints in the different molecular subtypes were analyzed. Finally, we established a m(6)A- and m(5)C-related lncRNA signature and a prognostic nomogram. RESULTS: We identified 141 m(6)A- and m(5)C-related lncRNAs by co-expression analysis, among which 23 lncRNAs were significantly associated with the overall survival (OS) of CRC patients. Two distinct molecular subtypes (cluster A and cluster B) were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, TIICs, immune checkpoints. Next, a m(6)A- and m(5)C-related lncRNA signature for predicting OS was constructed, and its predictive capability in CRC patients was validated. We then constructed a highly accurate nomogram for improving the clinical applicability of the signature. Analyses of clinicopathological features, prognosis, TIICs, cancer stem cell (CSC), and drug response revealed significant differences between two risk groups. In addition, we found that patients with a low-risk score exhibited enhanced response to anti-PD-1/L1 immunotherapy. Functional enrichment analysis showed that these lncRNAs related to the high-risk group were involved in the development and progression of CRC. CONCLUSIONS: We conducted a comprehensive analysis of m(6)A- and m(5)C-related lncRNAs in CRC and revealed their potential functions in predicting tumor-immune-stromal microenvironment, clinicopathological features, and prognosis, and determined their role in immunotherapy. These findings may improve our understanding of the cross-talk between m(6)A- and m(5)C-related lncRNAs in CRC and pave a new road for prognosis assessment and more effective immunotherapy strategies. Frontiers Media S.A. 2022-03-08 /pmc/articles/PMC8957790/ /pubmed/35350786 http://dx.doi.org/10.3389/fimmu.2022.740960 Text en Copyright © 2022 Song, Ren, Xiang, Yuan and Fu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Song, Wei
Ren, Jun
Xiang, Rensheng
Yuan, Wenzheng
Fu, Tao
Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
title Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
title_full Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
title_fullStr Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
title_full_unstemmed Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
title_short Cross-Talk Between m(6)A- and m(5)C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
title_sort cross-talk between m(6)a- and m(5)c-related lncrnas to construct a novel signature and predict the immune landscape of colorectal cancer patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957790/
https://www.ncbi.nlm.nih.gov/pubmed/35350786
http://dx.doi.org/10.3389/fimmu.2022.740960
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