Sun Zhuolun, Jing Changying, Guo Xudong, Zhang Mingxiao, Kong Feng, Wang Zhenqing, Jiang Shaobo, Wang Hanbo
Department of Urology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
School of Medicine, Technical University of Munich, Munich, Germany.
Front Oncol. 2021 Sep 9;11:716854. doi: 10.3389/fonc.2021.716854. eCollection 2021.
Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.
肾透明细胞癌(KIRC)长期以来一直被认为是一种具有高度免疫浸润的肿瘤。然而,细胞焦亡在KIRC肿瘤微环境(TME)中的潜在作用仍鲜为人知。在此,我们基于癌症基因组图谱(TCGA)数据库,系统地分析了KIRC患者中细胞焦亡相关基因(PRG)的预后价值、在TME中的作用、对免疫检查点抑制剂(ICI)的反应以及药物敏感性。通过对24个PRG进行一致性聚类,聚类2显示出较差的预后,这可能是因为与恶性肿瘤相关的特征显著富集。此外,我们构建了一个预后预测模型,该模型在高风险和低风险患者之间具有良好的区分能力,并在外部E-MTAB-1980队列和HSP队列中得到进一步验证。通过基于风险模型进一步分析TME,发现高风险组中免疫细胞浸润较高,肿瘤纯度较低,预后较差。高风险评分的患者也表现出较高的ICI表达,这表明这些患者可能更倾向于从ICI中获益。我们还确定了与模型相关基因相关的抗癌药物敏感性。总的来说,细胞焦亡相关的预后风险模型可能会改善预后信息,并为目前针对KIRC患者免疫治疗策略的研究提供方向。