Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, Liaoning, China.
Sci Rep. 2024 May 27;14(1):12044. doi: 10.1038/s41598-024-62978-0.
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.
这项研究针对的是肾透明细胞癌（ccRCC）尽管有多种治疗方法，但仍存在持续的预后和治疗挑战。我们关注的是细胞凋亡，这是肿瘤进展和转移中一种关键的程序性细胞死亡形式，研究了其在癌症进化中的抵抗性。通过对来自七个 ccRCC 患者的单细胞 RNA 测序，我们评估了与细胞凋亡相关的基因（ARGs）的影响，并在与细胞凋亡相关的上皮亚群（ARESs）中确定了差异表达的基因（DEGs）。此外，还分析了来自 GEO 数据库的六个 ccRCC RNA 微阵列数据集，以确定稳健的 DEGs。通过 LASSO 和多变量 Cox 回归开发了一个新的风险预后模型，并使用 BEST、ULCAN 和 RT-PCR 进行验证。该研究包括功能富集、肿瘤微环境（TME）中的免疫浸润分析以及药物敏感性评估，最终形成了一个整合临床参数的预测列线图。结果突出了 ARES 中 ARG 表达模式的动态变化和细胞间相互作用的增强，KEGG 途径在 MYC+上皮亚群中的显著富集表明细胞凋亡抵抗性增强。此外，所有的 ARESs 都在空间背景中被识别出来，并探讨了它们的位置关系。鉴定出三个关键的预后基因-TIMP1、PECAM1 和 CDKN1A，高风险组表现出更强的免疫浸润和细胞凋亡抵抗性，与预后较差相关。这项研究提供了一个新的 ccRCC 风险特征，为患者管理、预后和个性化治疗提供了创新的方法。
