解析透明细胞肾细胞癌的肿瘤微环境:基于机器学习的程序性死亡基因的预后见解。
Deciphering the tumour microenvironment of clear cell renal cell carcinoma: Prognostic insights from programmed death genes using machine learning.
机构信息
Department of Urology, Dazhou Central Hospital, Dazhou, Sichuan, China.
School of Clinical Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
出版信息
J Cell Mol Med. 2024 Jul;28(13):e18524. doi: 10.1111/jcmm.18524.
Clear cell renal cell carcinoma (ccRCC), a prevalent kidney cancer form characterised by its invasiveness and heterogeneity, presents challenges in late-stage prognosis and treatment outcomes. Programmed cell death mechanisms, crucial in eliminating cancer cells, offer substantial insights into malignant tumour diagnosis, treatment and prognosis. This study aims to provide a model based on 15 types of Programmed Cell Death-Related Genes (PCDRGs) for evaluating immune microenvironment and prognosis in ccRCC patients. ccRCC patients from the TCGA and arrayexpress cohorts were grouped based on PCDRGs. A combination model using Lasso and SuperPC was constructed to identify prognostic gene features. The arrayexpress cohort validated the model, confirming its robustness. Immune microenvironment analysis, facilitated by PCDRGs, employed various methods, including CIBERSORT. Drug sensitivity analysis guided clinical treatment decisions. Single-cell data enabled Programmed Cell Death-Related scoring, subsequent pseudo-temporal and cell-cell communication analyses. A PCDRGs signature was established using TCGA-KIRC data. External validation in the arrayexpress cohort underscored the model's superiority over traditional clinical features. Furthermore, our single-cell analysis unveiled the roles of PCDRG-based single-cell subgroups in ccRCC, both in pseudo-temporal progression and intercellular communication. Finally, we performed CCK-8 assay and other experiments to investigate csf2. In conclusion, these findings reveal that csf2 inhibit the growth, infiltration and movement of cells associated with renal clear cell carcinoma. This study introduces a PCDRGs prognostic model benefiting ccRCC patients while shedding light on the pivotal role of programmed cell death genes in shaping the immune microenvironment of ccRCC patients.
透明细胞肾细胞癌 (ccRCC) 是一种常见的肾癌形式,其特点是侵袭性和异质性,在晚期预后和治疗结果方面带来挑战。程序性细胞死亡机制在消除癌细胞方面至关重要,为恶性肿瘤的诊断、治疗和预后提供了重要的见解。本研究旨在基于 15 种程序性细胞死亡相关基因 (PCDRGs) 为 ccRCC 患者建立一个评估免疫微环境和预后的模型。根据 PCDRGs 将 TCGA 和 arrayexpress 队列中的 ccRCC 患者进行分组。使用 Lasso 和 SuperPC 构建组合模型,以识别预后基因特征。arrayexpress 队列验证了该模型,证实了其稳健性。通过 PCDRGs 进行免疫微环境分析,采用了包括 CIBERSORT 在内的各种方法。药物敏感性分析指导临床治疗决策。单细胞数据可进行程序性细胞死亡相关评分,随后进行伪时间和细胞间通讯分析。使用 TCGA-KIRC 数据建立 PCDRGs 特征。在 arrayexpress 队列中的外部验证突显了该模型优于传统临床特征的优势。此外,我们的单细胞分析揭示了基于 PCDRG 的单细胞亚群在 ccRCC 中的作用,包括伪时间进展和细胞间通讯。最后,我们进行了 CCK-8 测定和其他实验来研究 csf2。总之,这些发现表明 csf2 抑制与肾透明细胞癌相关的细胞的生长、浸润和运动。本研究介绍了一个 PCDRGs 预后模型,使 ccRCC 患者受益,同时揭示了程序性细胞死亡基因在塑造 ccRCC 患者免疫微环境中的关键作用。