尽管多模式疗法取得了进展，但这项研究解决了透明细胞肾细胞癌 (ccRCC) 持续存在的预后和管理挑战。我们重点关注失巢凋亡（肿瘤进展和转移中程序性细胞死亡的一种关键形式），研究了其在癌症进化中的抵抗力。利用七名 ccRCC 患者的单细胞 RNA 测序，我们评估了失巢凋亡相关基因 (ARG) 的影响，并鉴定了失巢凋亡相关上皮亚簇 (ARES) 中的差异表达基因 (DEG)。此外，还分析了 GEO 数据库中的 6 个 ccRCC RNA 微阵列数据集的稳健 DEG。通过 LASSO 和多元 Cox 回归开发了一种新型风险预测模型，并使用 BEST、ULCAN 和 RT-PCR 进行了验证。该研究包括功能丰富、肿瘤微环境 (TME) 中的免疫浸润分析和药物敏感性评估，从而得出整合临床参数的预测列线图。结果强调了 ARES 中的动态 ARG 表达模式和增强的细胞间相互作用，MYC  上皮亚簇中的 KEGG 通路显着富集，表明失巢凋亡抵抗力增强。此外，所有 ARES 均在空间背景下进行了识别，并探讨了它们的位置关系。确定了三个关键的预后基因——TIMP1、PECAM1和CDKN1A，高危人群表现出更大的免疫浸润和失巢凋亡抵抗力，与较差的预后相关。这项研究提供了一种新颖的 ccRCC 风险特征，为患者管理、预后和个性化治疗提供了创新方法。© 2024。作者。

This study tackles the persistent prognostic and management challenges of clear cell renal cell carcinoma (ccRCC), despite advancements in multimodal therapies. Focusing on anoikis, a critical form of programmed cell death in tumor progression and metastasis, we investigated its resistance in cancer evolution. Using single-cell RNA sequencing from seven ccRCC patients, we assessed the impact of anoikis-related genes (ARGs) and identified differentially expressed genes (DEGs) in Anoikis-related epithelial subclusters (ARESs). Additionally, six ccRCC RNA microarray datasets from the GEO database were analyzed for robust DEGs. A novel risk prognostic model was developed through LASSO and multivariate Cox regression, validated using BEST, ULCAN, and RT-PCR. The study included functional enrichment, immune infiltration analysis in the tumor microenvironment (TME), and drug sensitivity assessments, leading to a predictive nomogram integrating clinical parameters. Results highlighted dynamic ARG expression patterns and enhanced intercellular interactions in ARESs, with significant KEGG pathway enrichment in MYC + Epithelial subclusters indicating enhanced anoikis resistance. Additionally, all ARESs were identified in the spatial context, and their locational relationships were explored. Three key prognostic genes-TIMP1, PECAM1, and CDKN1A-were identified, with the high-risk group showing greater immune infiltration and anoikis resistance, linked to poorer prognosis. This study offers a novel ccRCC risk signature, providing innovative approaches for patient management, prognosis, and personalized treatment.© 2024. The Author(s).