N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma
Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Geno...
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.726369/full |
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| author | Tianming Ma Tianming Ma Xiaonan Wang Xiaonan Wang Jiawen Wang Jiawen Wang Xiaodong Liu Xiaodong Liu Shicong Lai Shicong Lai Wei Zhang Lingfeng Meng Lingfeng Meng Zijian Tian Zijian Tian Yaoguang Zhang Yaoguang Zhang |
| author_facet | Tianming Ma Tianming Ma Xiaonan Wang Xiaonan Wang Jiawen Wang Jiawen Wang Xiaodong Liu Xiaodong Liu Shicong Lai Shicong Lai Wei Zhang Lingfeng Meng Lingfeng Meng Zijian Tian Zijian Tian Yaoguang Zhang Yaoguang Zhang |
| author_sort | Tianming Ma |
| collection | DOAJ |
| description | Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC. |
| first_indexed | 2024-12-21T10:03:38Z |
| format | Article |
| id | doaj.art-90ece73e0d1b42bda598837740de884a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T10:03:38Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-90ece73e0d1b42bda598837740de884a2022-12-21T19:07:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.726369726369N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell CarcinomaTianming Ma0Tianming Ma1Xiaonan Wang2Xiaonan Wang3Jiawen Wang4Jiawen Wang5Xiaodong Liu6Xiaodong Liu7Shicong Lai8Shicong Lai9Wei Zhang10Lingfeng Meng11Lingfeng Meng12Zijian Tian13Zijian Tian14Yaoguang Zhang15Yaoguang Zhang16Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Radiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaIncreasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.https://www.frontiersin.org/articles/10.3389/fgene.2021.726369/fullclear-cell renal cell carcinomaN6-methyladenosinelncRNAprognostic signatureimmune infiltration |
| spellingShingle | Tianming Ma Tianming Ma Xiaonan Wang Xiaonan Wang Jiawen Wang Jiawen Wang Xiaodong Liu Xiaodong Liu Shicong Lai Shicong Lai Wei Zhang Lingfeng Meng Lingfeng Meng Zijian Tian Zijian Tian Yaoguang Zhang Yaoguang Zhang N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma Frontiers in Genetics clear-cell renal cell carcinoma N6-methyladenosine lncRNA prognostic signature immune infiltration |
| title | N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma |
| title_full | N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma |
| title_fullStr | N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma |
| title_full_unstemmed | N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma |
| title_short | N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma |
| title_sort | n6 methyladenosine related long non coding rna signature associated with prognosis and immunotherapeutic efficacy of clear cell renal cell carcinoma |
| topic | clear-cell renal cell carcinoma N6-methyladenosine lncRNA prognostic signature immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.726369/full |
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