Chen Jian, Zhu Cheng, He Yan, Huang Liping, Wang Weizhuo, Huang Shuaishuai
Medical Department, Ningbo Women and Children's Hospital, Ningbo, Zhejiang, China.
Center for Reproductive Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Discov Oncol. 2025 Jan 30;16(1):102. doi: 10.1007/s12672-025-01831-w.
Clear cell renal cell carcinoma (ccRCC) remains a challenging cancer type due to its resistance to standard treatments. Immunogenic cell death (ICD) has the potential to activate anti-tumor immunity, presenting a promising avenue for ccRCC therapies.
We analyzed data from GSE29609, TCGA-KIRC, and GSE159115 to identify ICD-related prognostic genes in ccRCC. By applying consensus clustering, patients were categorized based on ICD modification patterns, and an ICD signature (ICDS) model was developed using a PCA approach. Functional studies were conducted with FOXP3 knockdown in ccRCC cell lines to explore its impact on cell behavior.
Eleven ICD-related genes were identified as key prognostic indicators in ccRCC, with high ICDS linked to worse survival outcomes. High ICDS also correlated with increased levels of immune-suppressive cells within the tumor microenvironment. FOXP3 was highlighted as a critical gene influencing ICD, where its knockdown significantly reduced ccRCC cell proliferation and migration, underscoring its role in tumor progression.
This study establishes FOXP3 as a pivotal factor in ICD regulation and ccRCC progression. Targeting FOXP3 and other ICD pathways could enhance treatment efficacy in ccRCC, providing a foundation for ICD-based therapeutic strategies. Evaluating ICD patterns in ccRCC may guide patient-specific interventions, paving the way for improved management of this aggressive cancer.
透明细胞肾细胞癌（ccRCC）由于对标准治疗具有抗性，仍然是一种具有挑战性的癌症类型。免疫原性细胞死亡（ICD）有可能激活抗肿瘤免疫，为ccRCC治疗提供了一条有前景的途径。
我们分析了来自GSE29609、TCGA - KIRC和GSE159115的数据，以识别ccRCC中与ICD相关的预后基因。通过应用一致性聚类，根据ICD修饰模式对患者进行分类，并使用主成分分析（PCA）方法开发了一个ICD特征（ICDS）模型。在ccRCC细胞系中进行了FOXP3敲低的功能研究，以探讨其对细胞行为的影响。
11个与ICD相关的基因被确定为ccRCC的关键预后指标，高ICDS与较差的生存结果相关。高ICDS还与肿瘤微环境中免疫抑制细胞水平的增加相关。FOXP3被突出显示为影响ICD的关键基因，其敲低显著降低了ccRCC细胞的增殖和迁移，强调了其在肿瘤进展中的作用。
本研究确定FOXP3是ICD调节和ccRCC进展中的关键因素。靶向FOXP3和其他ICD途径可能提高ccRCC的治疗效果，为基于ICD的治疗策略提供基础。评估ccRCC中的ICD模式可能指导针对患者的干预措施，为改善这种侵袭性癌症的管理铺平道路。
