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Abstract：
BACKGROUND: Kidney cancer is an immunogenic solid tumor, characterized by high tumor burden and infiltration of CD8+ T cells. Although immunotherapy targeting the PD1/CTLA-4 axis has demonstrated excellent clinical efficacy, clinical outcomes in most patients are poor.
METHODS: We used the RNA sequencing data from the GEO database for KIRC GSE121636 and normal kidney tissue GSE131685, and performed single-cell analysis for cluster identification, pathway enrichment, and CD8+ T cell-associated gene identification. Subsequently, the significance of different CD8+ T-cell associated gene subtypes was elucidated by consensus clustering, pathway analysis, mutated gene analysis, and KIRC immune microenvironment analysis in the TCGA-KIRC disease cohort. Single gene analysis identified LAG3 as the most critical CD8+ T-cell-associated gene and its function was verified by cell phenotype and immunohistochemistry in KIRC.
RESULTS: In the present study, CD8+ T-cell associated genes in KIRC were screened, including GZMK, CD27, CCL4L2, FXYD2, LAG3, RGS1, CST7, DUSP4, CD8A, and TRBV20-1 and an immunological risk prognostic model was constructed (risk score = - 0.291858656434841*GZMK - 0.192758342489394*FXYD2 + 0.625023643446193*LAG3 + 0.161324477181591*RGS1 - 0.380169045328895*DUSP4 - 0.107221347575037*TRBV20-1). LAG3 was identified and proved as the most critical CD8+ T cell-associated gene in KIRC.
CONCLUSIONS: We proposed and constructed an immunological risk prognostic model for CD8+ T cell-associated genes and identified LAG3 as a pivotal gene for KIRC progression and CD8+ T-cell infiltration. The model comprehensively explained the immune microenvironment and provided novel immune-related therapeutic targets and biomarkers in KIRC.
METHODS: We used the RNA sequencing data from the GEO database for KIRC GSE121636 and normal kidney tissue GSE131685, and performed single-cell analysis for cluster identification, pathway enrichment, and CD8+ T cell-associated gene identification. Subsequently, the significance of different CD8+ T-cell associated gene subtypes was elucidated by consensus clustering, pathway analysis, mutated gene analysis, and KIRC immune microenvironment analysis in the TCGA-KIRC disease cohort. Single gene analysis identified LAG3 as the most critical CD8+ T-cell-associated gene and its function was verified by cell phenotype and immunohistochemistry in KIRC.
RESULTS: In the present study, CD8+ T-cell associated genes in KIRC were screened, including GZMK, CD27, CCL4L2, FXYD2, LAG3, RGS1, CST7, DUSP4, CD8A, and TRBV20-1 and an immunological risk prognostic model was constructed (risk score = - 0.291858656434841*GZMK - 0.192758342489394*FXYD2 + 0.625023643446193*LAG3 + 0.161324477181591*RGS1 - 0.380169045328895*DUSP4 - 0.107221347575037*TRBV20-1). LAG3 was identified and proved as the most critical CD8+ T cell-associated gene in KIRC.
CONCLUSIONS: We proposed and constructed an immunological risk prognostic model for CD8+ T cell-associated genes and identified LAG3 as a pivotal gene for KIRC progression and CD8+ T-cell infiltration. The model comprehensively explained the immune microenvironment and provided novel immune-related therapeutic targets and biomarkers in KIRC.
摘要：
背景：肾癌是一种免疫原性实体瘤，以高肿瘤负荷和CD8+T细胞浸润为特征。尽管针对PD1/CTLA-4轴的免疫治疗已显示出优异的临床疗效，大多数患者的临床结局较差.
方法：我们将来自GEO数据库的RNA测序数据用于KIRCGSE121636和正常肾组织GSE131685，并进行单细胞分析以进行簇识别，途径富集，和CD8+T细胞相关基因鉴定。随后，通过共识聚类阐明了不同CD8+T细胞相关基因亚型的意义，途径分析,突变基因分析，TCGA-KIRC疾病队列中的KIRC免疫微环境分析。单基因分析确定LAG3是最关键的CD8+T细胞相关基因，其功能在KIRC中通过细胞表型和免疫组织化学得到证实。
结果：在本研究中，筛选KIRC中CD8+T细胞相关基因,包括GZMK,CD27,CCL4L2,FXYD2,LAG3,RGS1,CST7,DUSP4,CD8A,和TRBV20-1并建立了免疫风险预后模型（风险评分=-0.291858656434841*GZMK-0.192758342489394*FXYD2+0.625023643446193*LAG3+0.161324477181591*RGS1-0.380169045328895*DUSP4-0.1072213475V737501LAG3被鉴定并证明是KIRC中最关键的CD8+T细胞相关基因。
结论：我们提出并构建了CD8+T细胞相关基因的免疫风险预测模型，并确定LAG3是KIRC进展和CD8+T细胞浸润的关键基因。该模型全面解释了免疫微环境，并在KIRC中提供了新的免疫相关治疗靶标和生物标志物。
方法：我们将来自GEO数据库的RNA测序数据用于KIRCGSE121636和正常肾组织GSE131685，并进行单细胞分析以进行簇识别，途径富集，和CD8+T细胞相关基因鉴定。随后，通过共识聚类阐明了不同CD8+T细胞相关基因亚型的意义，途径分析,突变基因分析，TCGA-KIRC疾病队列中的KIRC免疫微环境分析。单基因分析确定LAG3是最关键的CD8+T细胞相关基因，其功能在KIRC中通过细胞表型和免疫组织化学得到证实。
结果：在本研究中，筛选KIRC中CD8+T细胞相关基因,包括GZMK,CD27,CCL4L2,FXYD2,LAG3,RGS1,CST7,DUSP4,CD8A,和TRBV20-1并建立了免疫风险预后模型（风险评分=-0.291858656434841*GZMK-0.192758342489394*FXYD2+0.625023643446193*LAG3+0.161324477181591*RGS1-0.380169045328895*DUSP4-0.1072213475V737501LAG3被鉴定并证明是KIRC中最关键的CD8+T细胞相关基因。
结论：我们提出并构建了CD8+T细胞相关基因的免疫风险预测模型，并确定LAG3是KIRC进展和CD8+T细胞浸润的关键基因。该模型全面解释了免疫微环境，并在KIRC中提供了新的免疫相关治疗靶标和生物标志物。
