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...
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Elsevier
2023-09-01
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Series: | Translational Oncology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323001122 |
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author | Cheng-Peng Gui Jin-Huan Wei Chi Zhang Yi-Ming Tang Guan-Nan Shu Rong-Pei Wu Jun-Hang Luo |
author_facet | Cheng-Peng Gui Jin-Huan Wei Chi Zhang Yi-Ming Tang Guan-Nan Shu Rong-Pei Wu Jun-Hang Luo |
author_sort | Cheng-Peng Gui |
collection | DOAJ |
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. |
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language | English |
last_indexed | 2024-03-12T23:17:24Z |
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series | Translational Oncology |
spelling | doaj.art-696e429bb2f545a5b0cb3b9bf8c9419d2023-07-17T04:07:35ZengElsevierTranslational Oncology1936-52332023-09-0135101726Single-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 carcinomaCheng-Peng Gui0Jin-Huan Wei1Chi Zhang2Yi-Ming Tang3Guan-Nan Shu4Rong-Pei Wu5Jun-Hang Luo6Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Corresponding authors at: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR ChinaDepartment of Urology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR ChinaDepartment of Urology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR ChinaDepartment of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China; Corresponding authors at: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China; Institute of Precision Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China; Corresponding authors at: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.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.http://www.sciencedirect.com/science/article/pii/S1936523323001122Clear cell renal cell carcinomam5C RNA modificationSingle-cell transcriptomicsSpatial transcriptomicsTumor microenvironment |
spellingShingle | Cheng-Peng Gui Jin-Huan Wei Chi Zhang Yi-Ming Tang Guan-Nan Shu Rong-Pei Wu Jun-Hang Luo 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 Translational Oncology Clear cell renal cell carcinoma m5C RNA modification Single-cell transcriptomics Spatial transcriptomics Tumor microenvironment |
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 | Clear cell renal cell carcinoma m5C RNA modification Single-cell transcriptomics Spatial transcriptomics Tumor microenvironment |
url | http://www.sciencedirect.com/science/article/pii/S1936523323001122 |
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