肾细胞癌(RCC)代表了泌尿生殖系统癌症的重要部分,具有挑战性的预后和高转移率。免疫治疗已应用于晚期肾细胞癌的治疗,但治疗效果并不令人满意.在这项研究中,我们构建了与肾脏患者结局相关的Janus激酶/信号转导和转录激活因子(JAK/STAT)相关特征,以更好地预测免疫检查点抑制剂(ICIs)的疗效,并为有效的联合治疗提供指导.我们筛选了25个在RCC样品中表现出高表达并在JAK-STAT信号通路中富集的差异表达基因(DEGs)。在这些基因中,确定了11个关键基因,并与肾透明细胞癌(KIRC)患者的预期相关,与癌旁组织和正常肾细胞相比,所有这些基因在RCC肿瘤组织和癌细胞中均显着升高。利用这11个基因,我们将RCC患者分为高危组和低危组.我们发现KIRC患者的临床病理因素与JAK-STAT相关风险评分之间存在明显的相关性。且IHC结果显示,RCC患者肿瘤组织中JAK3和STAT4的表达明显高于正常组织,JAK3和STAT4水平与RCC患者T分期呈正相干。此外,高危患者预后较差,原瘤免疫细胞浸润较大,与低危患者相比,从免疫治疗中获益较少。此外,JAK-STAT相关风险评分可根据列线图预测RCC患者的无病生存期(DFS),结合其他临床特征,如年龄,TNM分期和分期。我们的研究证明了JAK-STAT信号通路在RCC肿瘤免疫中的重要调控功能。这种洞察力不仅增强了我们准确预测RCC患者生存率的能力,但也强调了RCC的潜在治疗替代方案,涉及JAK-STAT途径和免疫检查点的联合靶向。
Renal cell carcinoma (RCC) represents a significant portion of genitourinary cancers, marked by challenging prognosis and high metastasis rates. Immunotherapy has been applied in managing advanced renal cell carcinoma, but the therapeutic outcomes are unsatisfactory. In this study, we order to construct a Janus kinase/signal transduction and activator transcriptional (JAK/STAT)-related signature linked to kidney patient outcomes for better predicting the efficacy to immune checkpoint inhibitors (ICIs) and to provide guidance for effective combination therapy. We screened 25 differentially expressed genes (DEGs) that exhibited high expression in RCC samples and were enriched in the JAK-STAT signaling pathway. Among these genes, 11 key genes were identified and correlated with the expectation of Kidney Clear Cell Carcinoma (KIRC) patients and all these genes was significantly elevated in RCC tumor tissues and cancer cells compared to para-cancer tissues and normal renal cells. Utilizing these 11 genes, we divided RCC patients into high-risk and low-risk groups. We found a clear correlation between the clinicopathologic factors of KIRC patients and the JAK-STAT-related risk score. And the IHC results shown that the JAK3 and STAT4 expression of tumor was significantly higher than normal tissue in RCC patients, the level of JAK3 and STAT4 was positively related to the T stage of RCC patients. In addition, high-risk patients had a poorer prognosis and greater protumor immune cell infiltration, and benefitted less from immunotherapy than did low-risk patients. Furthermore, the JAK-STAT-related risk score can predict disease-free survival (DFS) in RCC patients according to the nomogram, which constructed in combination with other clinical features such as age, TNM-staging and stage. Our study demonstrated the JAK-STAT signaling pathway\'s important regulatory function in RCC tumor immunity. This insight not only enhances our ability to accurately predict the survival rate of RCC patients, but also underscores a potential therapeutic alternative for RCC, involving the combined targeting of the JAK-STAT pathway and immune checkpoints.