Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma
BackgroundImmunogenic cell death (ICD) is considered a particular cell death modality of regulated cell death (RCD) and plays a significant role in various cancers. The connection between kidney renal clear cell carcinoma (KIRC) and ICD remains to be thoroughly explored.MethodsWe conducted a variety...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1207061/full |
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| author | Silin Jiang Yuxiang Dong Jun Wang Xi Zhang Wei Liu Yong Wei Hai Zhou Luming Shen Jian Yang Qingyi Zhu |
| author_facet | Silin Jiang Yuxiang Dong Jun Wang Xi Zhang Wei Liu Yong Wei Hai Zhou Luming Shen Jian Yang Qingyi Zhu |
| author_sort | Silin Jiang |
| collection | DOAJ |
| description | BackgroundImmunogenic cell death (ICD) is considered a particular cell death modality of regulated cell death (RCD) and plays a significant role in various cancers. The connection between kidney renal clear cell carcinoma (KIRC) and ICD remains to be thoroughly explored.MethodsWe conducted a variety of bioinformatics analyses using R software, including cluster analysis, prognostic analysis, enrichment analysis and immune infiltration analysis. In addition, we performed Quantitative Real-time PCR to evaluate RNA levels of specific ICD genes. The proliferation was measured through Cell Counting Kit-8 (CCK-8) assay and colony-formation assay in RCC cell lines. ResultsWe determined two ICD subtypes through consensus clustering analysis. The two subtypes showed significantly different clinical outcomes, genomic alterations and tumor immune microenvironment. Moreover, we constructed the ICD prognostic signature based on TF, FOXP3, LY96, SLC7A11, HSP90AA1, UCN, IFNB1 and TLR3 and calculated the risk score for each patient. Kaplan-Meier survival analysis and ROC curve demonstrated that patients in the high-risk group had significantly poorer prognosis compared with the low-risk group. We then validated the signature through external cohort and further evaluated the relation between the signature and clinical features, tumor immune microenvironment and immunotherapy response. Given its critical role in ICD, we conducted further analysis on LY96. Our results indicated that downregulation of LY96 inhibited the proliferation ability of RCC cells.ConclusionsOur research revealed the underlying function of ICD in KIRC and screened out a potential biomarker, which provided a novel insight into individualized immunotherapy in KIRC. |
| first_indexed | 2024-03-12T14:22:27Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T14:22:27Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-7651585f0e63416384f42db85c2d750d2023-08-18T14:13:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12070611207061Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinomaSilin Jiang0Yuxiang Dong1Jun Wang2Xi Zhang3Wei Liu4Yong Wei5Hai Zhou6Luming Shen7Jian Yang8Qingyi Zhu9Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, Nanjing University of Chinese Medicine, Nanjing, ChinaThe State Key Lab of Reproductive; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackgroundImmunogenic cell death (ICD) is considered a particular cell death modality of regulated cell death (RCD) and plays a significant role in various cancers. The connection between kidney renal clear cell carcinoma (KIRC) and ICD remains to be thoroughly explored.MethodsWe conducted a variety of bioinformatics analyses using R software, including cluster analysis, prognostic analysis, enrichment analysis and immune infiltration analysis. In addition, we performed Quantitative Real-time PCR to evaluate RNA levels of specific ICD genes. The proliferation was measured through Cell Counting Kit-8 (CCK-8) assay and colony-formation assay in RCC cell lines. ResultsWe determined two ICD subtypes through consensus clustering analysis. The two subtypes showed significantly different clinical outcomes, genomic alterations and tumor immune microenvironment. Moreover, we constructed the ICD prognostic signature based on TF, FOXP3, LY96, SLC7A11, HSP90AA1, UCN, IFNB1 and TLR3 and calculated the risk score for each patient. Kaplan-Meier survival analysis and ROC curve demonstrated that patients in the high-risk group had significantly poorer prognosis compared with the low-risk group. We then validated the signature through external cohort and further evaluated the relation between the signature and clinical features, tumor immune microenvironment and immunotherapy response. Given its critical role in ICD, we conducted further analysis on LY96. Our results indicated that downregulation of LY96 inhibited the proliferation ability of RCC cells.ConclusionsOur research revealed the underlying function of ICD in KIRC and screened out a potential biomarker, which provided a novel insight into individualized immunotherapy in KIRC.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1207061/fullimmunogenic cell deathkidney renal clear cell carcinomatumor immune microenvironmentprognostic signatureimmunotherapy |
| spellingShingle | Silin Jiang Yuxiang Dong Jun Wang Xi Zhang Wei Liu Yong Wei Hai Zhou Luming Shen Jian Yang Qingyi Zhu Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma Frontiers in Immunology immunogenic cell death kidney renal clear cell carcinoma tumor immune microenvironment prognostic signature immunotherapy |
| title | Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma |
| title_full | Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma |
| title_fullStr | Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma |
| title_full_unstemmed | Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma |
| title_short | Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma |
| title_sort | identification of immunogenic cell death related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma |
| topic | immunogenic cell death kidney renal clear cell carcinoma tumor immune microenvironment prognostic signature immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1207061/full |
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