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Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma
Clear cell Renal Cell Carcinoma (ccRCC) is a highly heterogeneous disease, making it challenging to predict prognosis and therapy efficacy. In this study, we aimed to explore the role of 5-methylcytosine (m5C) RNA modification in ccRCC and its potential as a predictor for therapy response and overal...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316128/ https://www.ncbi.nlm.nih.gov/pubmed/37379773 http://dx.doi.org/10.1016/j.tranon.2023.101726 |
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author | Gui, Cheng-Peng Wei, Jin-Huan Zhang, Chi Tang, Yi-Ming Shu, Guan-Nan Wu, Rong-Pei Luo, Jun-Hang |
author_facet | Gui, Cheng-Peng Wei, Jin-Huan Zhang, Chi Tang, Yi-Ming Shu, Guan-Nan Wu, Rong-Pei Luo, Jun-Hang |
author_sort | Gui, Cheng-Peng |
collection | PubMed |
description | Clear cell Renal Cell Carcinoma (ccRCC) is a highly heterogeneous disease, making it challenging to predict prognosis and therapy efficacy. In this study, we aimed to explore the role of 5-methylcytosine (m5C) RNA modification in ccRCC and its potential as a predictor for therapy response and overall survival (OS). We established a novel 5-methylcytosine RNA modification-related gene index (M5CRMRGI) and studied its effect on the tumor microenvironment (TME) using single-cell sequencing data for in-depth analysis, and verified it using spatial sequencing data. Our results showed that M5CRMRGI is an independent predictor of OS in multiple datasets and exhibited outstanding performance in predicting the OS of ccRCC. Distinct mutation profiles, hallmark pathways, and infiltration of immune cells in TME were observed between high- and low-M5CRMRGI groups. Single-cell/spatial transcriptomics revealed that M5CRMRGI could reprogram the distribution of tumor-infiltrating immune cells. Moreover, significant differences in tumor immunogenicity and tumor immune dysfunction and exclusion (TIDE) were observed between the two risk groups, suggesting a better response to immune checkpoint blockade therapy of the high-risk group. We also predicted six potential drugs binding to the core target of the M5CRMRGI signature via molecular docking. Real-world treatment cohort data proved once again that high-risk patients were appropriate for immune checkpoint blockade therapy, while low-risk patients were appropriate for Everolimus. Our study shows that the m5C modification landscape plays a role in TME distribution. The proposed M5CRMRGI-guided strategy for predicting survival and immunotherapy efficacy, we reported here, might also be applied to more cancers other than ccRCC. |
format | Online Article Text |
id | pubmed-10316128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103161282023-07-04 Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma Gui, Cheng-Peng Wei, Jin-Huan Zhang, Chi Tang, Yi-Ming Shu, Guan-Nan Wu, Rong-Pei Luo, Jun-Hang Transl Oncol Original Research Clear cell Renal Cell Carcinoma (ccRCC) is a highly heterogeneous disease, making it challenging to predict prognosis and therapy efficacy. In this study, we aimed to explore the role of 5-methylcytosine (m5C) RNA modification in ccRCC and its potential as a predictor for therapy response and overall survival (OS). We established a novel 5-methylcytosine RNA modification-related gene index (M5CRMRGI) and studied its effect on the tumor microenvironment (TME) using single-cell sequencing data for in-depth analysis, and verified it using spatial sequencing data. Our results showed that M5CRMRGI is an independent predictor of OS in multiple datasets and exhibited outstanding performance in predicting the OS of ccRCC. Distinct mutation profiles, hallmark pathways, and infiltration of immune cells in TME were observed between high- and low-M5CRMRGI groups. Single-cell/spatial transcriptomics revealed that M5CRMRGI could reprogram the distribution of tumor-infiltrating immune cells. Moreover, significant differences in tumor immunogenicity and tumor immune dysfunction and exclusion (TIDE) were observed between the two risk groups, suggesting a better response to immune checkpoint blockade therapy of the high-risk group. We also predicted six potential drugs binding to the core target of the M5CRMRGI signature via molecular docking. Real-world treatment cohort data proved once again that high-risk patients were appropriate for immune checkpoint blockade therapy, while low-risk patients were appropriate for Everolimus. Our study shows that the m5C modification landscape plays a role in TME distribution. The proposed M5CRMRGI-guided strategy for predicting survival and immunotherapy efficacy, we reported here, might also be applied to more cancers other than ccRCC. Neoplasia Press 2023-06-26 /pmc/articles/PMC10316128/ /pubmed/37379773 http://dx.doi.org/10.1016/j.tranon.2023.101726 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Gui, Cheng-Peng Wei, Jin-Huan Zhang, Chi Tang, Yi-Ming Shu, Guan-Nan Wu, Rong-Pei Luo, Jun-Hang Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
title | Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
title_full | Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
title_fullStr | Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
title_full_unstemmed | Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
title_short | Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
title_sort | single-cell and spatial transcriptomics reveal 5-methylcytosine rna methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316128/ https://www.ncbi.nlm.nih.gov/pubmed/37379773 http://dx.doi.org/10.1016/j.tranon.2023.101726 |
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