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Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer
BACKGROUND: The prognosis of tumor patients can be assessed by measuring the levels of lncRNAs (long non-coding RNAs), which play a role in controlling the methylation of the RNA. Prognosis in individuals with colorectal adenocarcinoma (CRC) is strongly linked to lncRNA expression, making it imperat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481501/ https://www.ncbi.nlm.nih.gov/pubmed/37670275 http://dx.doi.org/10.1186/s12935-023-03025-2 |
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author | Di, Ziyang Xu, Gaoran Ding, Zheyu Li, Chengxin Song, Jialin Huang, Guoquan Zheng, Jinsen Zhang, Xinyao Xiong, Bin |
author_facet | Di, Ziyang Xu, Gaoran Ding, Zheyu Li, Chengxin Song, Jialin Huang, Guoquan Zheng, Jinsen Zhang, Xinyao Xiong, Bin |
author_sort | Di, Ziyang |
collection | PubMed |
description | BACKGROUND: The prognosis of tumor patients can be assessed by measuring the levels of lncRNAs (long non-coding RNAs), which play a role in controlling the methylation of the RNA. Prognosis in individuals with colorectal adenocarcinoma (CRC) is strongly linked to lncRNA expression, making it imperative to find lncRNAs that are associated with RNA methylation with strong prognostic value. METHODS: In this study, by analyzing TCGA dataset, we were able to develop a risk model for lncRNAs that are associated with m5C with prognostic significance by employing LASSO regression and univariate Cox proportional analysis. There were a number of methods employed to ensure the model was accurate, including multivariate and univariate Cox regression analysis, Kaplan analysis, and receiver operating characteristic curve analysis. The principal component analysis, GSEA and GSVA analysis were used for risk model analysis. The CIBERSORT instrument and the TIMER database were used to evaluate the link between the immune cells that infiltrate tumors and the risk model. In vitro experiments were also performed to validate the predicted m5C-related significant lncRNAs. RESULTS: The m5c regulators were differentially expressed in colorectal cancer and normal tissue. Based on the screening criteria and LASSO regression, 11 m5c-related lncRNAs were identified for developing the prognostic risk model. Multivariate and univariate Cox regression analysis showed the risk score is a crucial prognostic factor in CRC patients. The 1-year, 3-year, and 5-year AUC curves showed the risk score was higher than those identified for other clinicopathological characteristics. A nomogram using the risk score as a quantitative tool was developed for predicting patients' outcomes in clinical settings. In addition, the risk profile of m5C-associated lncRNAs can discriminate between tumor immune cells’ characteristics in CRC. Mutation patterns and chemotherapy were analyzed between high- and low- risk groups of CRC patients. Moreover, TNFRSF10A-AS1 was chosen for the in vitro verification of the m5C-connected lncRNA to demonstrate impressive effects on the proliferation, migration and invasion of CRC cells. CONCLUSION: A risk model including the prognostic value of 11 m5C-associated lncRNAs proves to be a useful prognostic tool for CRC and improves the care of patients suffering from CRC based on these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03025-2. |
format | Online Article Text |
id | pubmed-10481501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104815012023-09-07 Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer Di, Ziyang Xu, Gaoran Ding, Zheyu Li, Chengxin Song, Jialin Huang, Guoquan Zheng, Jinsen Zhang, Xinyao Xiong, Bin Cancer Cell Int Research BACKGROUND: The prognosis of tumor patients can be assessed by measuring the levels of lncRNAs (long non-coding RNAs), which play a role in controlling the methylation of the RNA. Prognosis in individuals with colorectal adenocarcinoma (CRC) is strongly linked to lncRNA expression, making it imperative to find lncRNAs that are associated with RNA methylation with strong prognostic value. METHODS: In this study, by analyzing TCGA dataset, we were able to develop a risk model for lncRNAs that are associated with m5C with prognostic significance by employing LASSO regression and univariate Cox proportional analysis. There were a number of methods employed to ensure the model was accurate, including multivariate and univariate Cox regression analysis, Kaplan analysis, and receiver operating characteristic curve analysis. The principal component analysis, GSEA and GSVA analysis were used for risk model analysis. The CIBERSORT instrument and the TIMER database were used to evaluate the link between the immune cells that infiltrate tumors and the risk model. In vitro experiments were also performed to validate the predicted m5C-related significant lncRNAs. RESULTS: The m5c regulators were differentially expressed in colorectal cancer and normal tissue. Based on the screening criteria and LASSO regression, 11 m5c-related lncRNAs were identified for developing the prognostic risk model. Multivariate and univariate Cox regression analysis showed the risk score is a crucial prognostic factor in CRC patients. The 1-year, 3-year, and 5-year AUC curves showed the risk score was higher than those identified for other clinicopathological characteristics. A nomogram using the risk score as a quantitative tool was developed for predicting patients' outcomes in clinical settings. In addition, the risk profile of m5C-associated lncRNAs can discriminate between tumor immune cells’ characteristics in CRC. Mutation patterns and chemotherapy were analyzed between high- and low- risk groups of CRC patients. Moreover, TNFRSF10A-AS1 was chosen for the in vitro verification of the m5C-connected lncRNA to demonstrate impressive effects on the proliferation, migration and invasion of CRC cells. CONCLUSION: A risk model including the prognostic value of 11 m5C-associated lncRNAs proves to be a useful prognostic tool for CRC and improves the care of patients suffering from CRC based on these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03025-2. BioMed Central 2023-09-05 /pmc/articles/PMC10481501/ /pubmed/37670275 http://dx.doi.org/10.1186/s12935-023-03025-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Di, Ziyang Xu, Gaoran Ding, Zheyu Li, Chengxin Song, Jialin Huang, Guoquan Zheng, Jinsen Zhang, Xinyao Xiong, Bin Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer |
title | Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer |
title_full | Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer |
title_fullStr | Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer |
title_full_unstemmed | Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer |
title_short | Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer |
title_sort | identification and validation of a novel prognosis model based on m5c-related long non-coding rnas in colorectal cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481501/ https://www.ncbi.nlm.nih.gov/pubmed/37670275 http://dx.doi.org/10.1186/s12935-023-03025-2 |
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