Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma
As the dominant histological subtype of kidney cancer, clear cell renal cell carcinoma (ccRCC) poorly responds to conventional chemotherapy and radiotherapy. Although novel immunotherapies such as immune checkpoint inhibitors could have a durable effect in treating ccRCC patients, the limited availa...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023029006 |
| _version_ | 1797815644166553600 |
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| author | Yanlin Tang Changzheng Zhang Chujin Ye Kaiwen Tian Jiayi Zeng Shouyu Cheng Weinan Zeng Bowen Yang Yanjun Liu Yuming Yu |
| author_facet | Yanlin Tang Changzheng Zhang Chujin Ye Kaiwen Tian Jiayi Zeng Shouyu Cheng Weinan Zeng Bowen Yang Yanjun Liu Yuming Yu |
| author_sort | Yanlin Tang |
| collection | DOAJ |
| description | As the dominant histological subtype of kidney cancer, clear cell renal cell carcinoma (ccRCC) poorly responds to conventional chemotherapy and radiotherapy. Although novel immunotherapies such as immune checkpoint inhibitors could have a durable effect in treating ccRCC patients, the limited availability of dependable biomarkers has restricted their application in clinic. In the study of carcinogenesis and cancer therapies, there has been a recent emphasis on researching programmed cell death (PCD). In the current study, we discovered the enriched and prognostic PCD in ccRCC utilizing gene set enrichment analysis (GSEA) and investigate the functional status of ccRCC patients with different PCD risks. Then, genes related to PCD that had prognostic value in ccRCC were identified for the conduction of non-negative matrix factorization to cluster ccRCC patients. Next, the tumor microenvironment, immunogenicity, and therapeutic response in different molecular clusters were analyzed. Among PCD, apoptosis and pyroptosis were enriched in ccRCC and correlated with prognosis. Patients with high PCD levels were related to poor prognosis and a rich but suppressive immune microenvironment. PCD-based molecular clusters were identified to differentiate the clinical status and prognosis of ccRCC. Moreover, the molecular cluster with high PCD levels may correlate with high immunogenicity and a favorable therapeutic response to ccRCC. Furthermore, a simplified PCD-based gene classifier was established to facilitate clinical application and used transcriptome sequencing data from clinical ccRCC samples to validate the applicability of the gene classifier. We thoroughly extended the understanding of PCD in ccRCC and constructed a PCD-based gene classifier for differentiation of the prognosis and therapeutic efficacy in ccRCC. |
| first_indexed | 2024-03-13T08:25:54Z |
| format | Article |
| id | doaj.art-8f18ed3d3d2648669c99afc0c9f99f36 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:25:54Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8f18ed3d3d2648669c99afc0c9f99f362023-05-31T04:45:11ZengElsevierHeliyon2405-84402023-05-0195e15693Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinomaYanlin Tang0Changzheng Zhang1Chujin Ye2Kaiwen Tian3Jiayi Zeng4Shouyu Cheng5Weinan Zeng6Bowen Yang7Yanjun Liu8Yuming Yu9Department of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Shantou University Medical College, Shantou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Shantou University Medical College, Shantou, ChinaDepartment of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou, China; Corresponding author.Department of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China; Corresponding author. Department of Urology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.As the dominant histological subtype of kidney cancer, clear cell renal cell carcinoma (ccRCC) poorly responds to conventional chemotherapy and radiotherapy. Although novel immunotherapies such as immune checkpoint inhibitors could have a durable effect in treating ccRCC patients, the limited availability of dependable biomarkers has restricted their application in clinic. In the study of carcinogenesis and cancer therapies, there has been a recent emphasis on researching programmed cell death (PCD). In the current study, we discovered the enriched and prognostic PCD in ccRCC utilizing gene set enrichment analysis (GSEA) and investigate the functional status of ccRCC patients with different PCD risks. Then, genes related to PCD that had prognostic value in ccRCC were identified for the conduction of non-negative matrix factorization to cluster ccRCC patients. Next, the tumor microenvironment, immunogenicity, and therapeutic response in different molecular clusters were analyzed. Among PCD, apoptosis and pyroptosis were enriched in ccRCC and correlated with prognosis. Patients with high PCD levels were related to poor prognosis and a rich but suppressive immune microenvironment. PCD-based molecular clusters were identified to differentiate the clinical status and prognosis of ccRCC. Moreover, the molecular cluster with high PCD levels may correlate with high immunogenicity and a favorable therapeutic response to ccRCC. Furthermore, a simplified PCD-based gene classifier was established to facilitate clinical application and used transcriptome sequencing data from clinical ccRCC samples to validate the applicability of the gene classifier. We thoroughly extended the understanding of PCD in ccRCC and constructed a PCD-based gene classifier for differentiation of the prognosis and therapeutic efficacy in ccRCC.http://www.sciencedirect.com/science/article/pii/S2405844023029006Clear cell renal cell carcinomaProgrammed cell deathGene expressionTumor microenvironmentImmunotherapy |
| spellingShingle | Yanlin Tang Changzheng Zhang Chujin Ye Kaiwen Tian Jiayi Zeng Shouyu Cheng Weinan Zeng Bowen Yang Yanjun Liu Yuming Yu Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma Heliyon Clear cell renal cell carcinoma Programmed cell death Gene expression Tumor microenvironment Immunotherapy |
| title | Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma |
| title_full | Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma |
| title_fullStr | Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma |
| title_full_unstemmed | Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma |
| title_short | Construction and validation of programmed cell death-based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma |
| title_sort | construction and validation of programmed cell death based molecular clusters for prognostic and therapeutic significance of clear cell renal cell carcinoma |
| topic | Clear cell renal cell carcinoma Programmed cell death Gene expression Tumor microenvironment Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023029006 |
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