As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner
Abstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system and the existing immunotherapy has not achieved satisfactory outcomes. Therefore, this study aims at establishing a novel gene signature for immune infiltration and clinical outco...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-022-02480-7 |
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| author | Daojia Miao Jian Shi Zhiyong Xiong Wen Xiao Xiangui Meng Qingyang Lv Kairu Xie Hongmei Yang Xiaoping Zhang |
| author_facet | Daojia Miao Jian Shi Zhiyong Xiong Wen Xiao Xiangui Meng Qingyang Lv Kairu Xie Hongmei Yang Xiaoping Zhang |
| author_sort | Daojia Miao |
| collection | DOAJ |
| description | Abstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system and the existing immunotherapy has not achieved satisfactory outcomes. Therefore, this study aims at establishing a novel gene signature for immune infiltration and clinical outcome (overall survival and immunotherapy responsiveness) in ccRCC patients. Methods Based on RNA sequencing data and clinical information in The Cancer Genome Atlas (TCGA) database, we calculated proportions of immune cells in 611 samples using an online tool CIBERSORTx. Multivariate survival analysis was conducted to determine crucial survival-associated immune cells and immune-infiltration-related genes (IIRGs). Next, the clinical specimens and common renal cancer cell lines were applied to confirm IIRGs expression at protein and RNA levels. Finally, functional enrichment analyses and siRNA technology targeted to RUFY4 were implemented to verify its function of predicting immunotherapy response. Results Follicular helper T cells (TFHs) and Regulatory T cells (Tregs) were highly infiltrated in the tumor microenvironment (TME) and their relative proportions were independent prognostic factors for patients. Among IIRGs of TFHs and TREGs, RUFY4 was found to be highly activated in tumor microenvironment and its co-expression network was enriched in PDL1/PD1 checkpoint pathway in cancer. Additionally, knockdown of RUFY4 led to the decline of PDL1 and proliferation ability in ccRCC cell lines. Conclusion TFHs and Tregs were considered as prognostic biomarkers and RUFY4 was an immunotherapeutic predictor of ccRCC patients in a PDL1-Related manner. |
| first_indexed | 2024-12-13T01:29:20Z |
| format | Article |
| id | doaj.art-4dbafbce72af4de1a1ae3b010e32ef9b |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T01:29:20Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-4dbafbce72af4de1a1ae3b010e32ef9b2022-12-22T00:04:03ZengBMCCancer Cell International1475-28672022-02-0122111610.1186/s12935-022-02480-7As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related mannerDaojia Miao0Jian Shi1Zhiyong Xiong2Wen Xiao3Xiangui Meng4Qingyang Lv5Kairu Xie6Hongmei Yang7Xiaoping Zhang8Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and TechnologyDepartment of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system and the existing immunotherapy has not achieved satisfactory outcomes. Therefore, this study aims at establishing a novel gene signature for immune infiltration and clinical outcome (overall survival and immunotherapy responsiveness) in ccRCC patients. Methods Based on RNA sequencing data and clinical information in The Cancer Genome Atlas (TCGA) database, we calculated proportions of immune cells in 611 samples using an online tool CIBERSORTx. Multivariate survival analysis was conducted to determine crucial survival-associated immune cells and immune-infiltration-related genes (IIRGs). Next, the clinical specimens and common renal cancer cell lines were applied to confirm IIRGs expression at protein and RNA levels. Finally, functional enrichment analyses and siRNA technology targeted to RUFY4 were implemented to verify its function of predicting immunotherapy response. Results Follicular helper T cells (TFHs) and Regulatory T cells (Tregs) were highly infiltrated in the tumor microenvironment (TME) and their relative proportions were independent prognostic factors for patients. Among IIRGs of TFHs and TREGs, RUFY4 was found to be highly activated in tumor microenvironment and its co-expression network was enriched in PDL1/PD1 checkpoint pathway in cancer. Additionally, knockdown of RUFY4 led to the decline of PDL1 and proliferation ability in ccRCC cell lines. Conclusion TFHs and Tregs were considered as prognostic biomarkers and RUFY4 was an immunotherapeutic predictor of ccRCC patients in a PDL1-Related manner.https://doi.org/10.1186/s12935-022-02480-7Clear cell renal cell carcinomaImmune infiltrationImmunotherapyPD-1 blockadePrognostic signatures |
| spellingShingle | Daojia Miao Jian Shi Zhiyong Xiong Wen Xiao Xiangui Meng Qingyang Lv Kairu Xie Hongmei Yang Xiaoping Zhang As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner Cancer Cell International Clear cell renal cell carcinoma Immune infiltration Immunotherapy PD-1 blockade Prognostic signatures |
| title | As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner |
| title_full | As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner |
| title_fullStr | As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner |
| title_full_unstemmed | As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner |
| title_short | As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner |
| title_sort | as a prognostic biomarker of clear cell renal cell carcinoma rufy4 predicts immunotherapy responsiveness in a pdl1 related manner |
| topic | Clear cell renal cell carcinoma Immune infiltration Immunotherapy PD-1 blockade Prognostic signatures |
| url | https://doi.org/10.1186/s12935-022-02480-7 |
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