Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma

被引:5
作者
Jiang, Silin [1 ]
Dong, Yuxiang [1 ]
Wang, Jun [2 ]
Zhang, Xi [3 ]
Liu, Wei [1 ]
Wei, Yong [1 ]
Zhou, Hai [1 ]
Shen, Luming [1 ]
Yang, Jian [1 ]
Zhu, Qingyi [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 2, Dept Urol, Nanjing, Peoples R China
[2] Nanjing Univ Chinese Med, Dept Urol, Nanjing, Peoples R China
[3] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, State Key Lab Reprod, Nanjing, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
immunogenic cell death; kidney renal clear cell carcinoma; tumor immune microenvironment; prognostic signature; immunotherapy;
D O I
10.3389/fimmu.2023.1207061
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:16
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