PDF(Pubmed)
Abstract：
Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.
摘要：
肾透明细胞癌（KIRC），肾癌的主要形式，对免疫检查点抑制剂（ICIs）表现出不同的治疗反应，强调ICI疗效预测模型的必要性。我们的研究建立了基于13种类型的程序性细胞死亡（PCD）的预后模型，与肿瘤进展和免疫微环境交织在一起。通过对综合数据集的分析进行验证，该模型鉴定出7个关键PCD基因,这些基因描述了两种具有不同免疫谱和对抗PD-1治疗敏感性的亚型.高PCD组表现出更具免疫抑制性的环境，而低PCD组对PD-1治疗表现出更好的反应。特别是,TOP2A成为至关重要的，其抑制作用显着降低KIRC细胞的生长和移动性。这些发现强调了PCDs在预测KIRC结果和免疫治疗反应方面的相关性，对加强临床决策具有重要意义。
