Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be criticall...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1046790/full |
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| author | Yulin Deng Kai Guo Zhenfeng Tang Yuanfa Feng Shanghua Cai Shanghua Cai Jianheng Ye Yuanxue Xi Jinchuang Li Ren Liu Chao Cai Zeheng Tan Yixun Zhang Zhaodong Han Guohua Zeng Weide Zhong Weide Zhong Weide Zhong Weide Zhong |
| author_facet | Yulin Deng Kai Guo Zhenfeng Tang Yuanfa Feng Shanghua Cai Shanghua Cai Jianheng Ye Yuanxue Xi Jinchuang Li Ren Liu Chao Cai Zeheng Tan Yixun Zhang Zhaodong Han Guohua Zeng Weide Zhong Weide Zhong Weide Zhong Weide Zhong |
| author_sort | Yulin Deng |
| collection | DOAJ |
| description | Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The “CIBERSORT” R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis. |
| first_indexed | 2024-04-12T06:45:31Z |
| format | Article |
| id | doaj.art-110fbdf2ed484288a94b3a096f68fb82 |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T06:45:31Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-110fbdf2ed484288a94b3a096f68fb822022-12-22T03:43:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10467901046790Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinomaYulin Deng0Kai Guo1Zhenfeng Tang2Yuanfa Feng3Shanghua Cai4Shanghua Cai5Jianheng Ye6Yuanxue Xi7Jinchuang Li8Ren Liu9Chao Cai10Zeheng Tan11Yixun Zhang12Zhaodong Han13Guohua Zeng14Weide Zhong15Weide Zhong16Weide Zhong17Weide Zhong18Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou Laboratory, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou Laboratory, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, ChinaState Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, Macau SAR, ChinaClear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The “CIBERSORT” R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1046790/fulltumor-infiltrating lymphocyteslong noncoding RNAbioinformaticsclear cell renal cell carcinomaprognostic |
| spellingShingle | Yulin Deng Kai Guo Zhenfeng Tang Yuanfa Feng Shanghua Cai Shanghua Cai Jianheng Ye Yuanxue Xi Jinchuang Li Ren Liu Chao Cai Zeheng Tan Yixun Zhang Zhaodong Han Guohua Zeng Weide Zhong Weide Zhong Weide Zhong Weide Zhong Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma Frontiers in Immunology tumor-infiltrating lymphocytes long noncoding RNA bioinformatics clear cell renal cell carcinoma prognostic |
| title | Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma |
| title_full | Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma |
| title_fullStr | Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma |
| title_full_unstemmed | Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma |
| title_short | Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma |
| title_sort | identification and experimental validation of a tumor infiltrating lymphocytes related long noncoding rna signature for prognosis of clear cell renal cell carcinoma |
| topic | tumor-infiltrating lymphocytes long noncoding RNA bioinformatics clear cell renal cell carcinoma prognostic |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1046790/full |
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