整合 scRNA 和 bulk-RNA 测序为分析肾透明细胞癌肿瘤异质性开发了细胞衰老特征。

INTRODUCTION: Cellular senescence (CS) plays a critical role in cancer development, including clear cell renal cell carcinoma (ccRCC). Traditional RNA sequencing cannot detect precise molecular composition changes within tumors. This study aimed to analyze cellular senescence's biochemical characteristics in ccRCC using single RNA sequencing (ScRNA-seq) and traditional RNA sequencing (Bulk RNA-seq). METHODS: Researchers analyzed the biochemical characteristics of cellular senescence in ccRCC using ScRNA-seq and Bulk RNA-seq. They combined these approaches to identify differences between malignant and non-malignant phenotypes in ccRCC across three senescence-related pathways. Genes from these pathways were used to identify molecular subtypes associated with senescence, and a new risk model was constructed. The function of the gene DUSP1 in ccRCC was validated through biological experiments. RESULTS: The combined analysis of ScRNA-seq and Bulk RNA-seq revealed significant differences between malignant and non-malignant phenotypes in ccRCC across three senescence-related pathways. Researchers identified genes from these pathways to identify molecular subtypes associated with senescence, constructing a new risk model. Different subgroups showed significant differences in prognosis level, clinical stage and grade, immune infiltration, immunotherapy, and drug sensitivity. DISCUSSION: Senescence signature markers are practical biomarkers and predictors of molecular typing in ccRCC. Differences in prognosis level, clinical stage and grade, immune infiltration, immunotherapy, and drug sensitivity between different subgroups indicate that this approach could provide valuable insights into senescence-related treatment options and prognostic assessment for patients with ccRCC. The function of the gene DUSP1 in ccRCC was validated through biological experiments, confirming its feasibility as a novel biomarker for ccRCC. These findings suggest that targeted therapies based on senescence-related mechanisms could be an effective treatment option for ccRCC.

简介：细胞衰老（CS）在癌症发展中起着关键作用，包括透明细胞肾细胞癌（ccRCC）。传统的 RNA 测序无法检测肿瘤内精确的分子组成变化。本研究旨在使用单细胞 RNA 测序（ScRNA-seq）和传统 RNA 测序（Bulk RNA-seq）分析 ccRCC 中细胞衰老的生化特征。

方法：研究人员使用 ScRNA-seq 和 Bulk RNA-seq 分析了 ccRCC 中细胞衰老的生化特征。他们将这些方法结合起来，鉴定了三个与衰老相关途径中 ccRCC 的恶性和非恶性表型之间的差异。这些途径中的基因用于鉴定与衰老相关的分子亚型，并构建了一个新的风险模型。通过生物学实验验证了基因 DUSP1 在 ccRCC 中的功能。

结果：ScRNA-seq 和 Bulk RNA-seq 的联合分析揭示了三个与衰老相关途径中 ccRCC 的恶性和非恶性表型之间的显著差异。研究人员从这些途径中鉴定出与衰老相关的基因，构建了一个新的风险模型。不同亚组在预后水平、临床分期和分级、免疫浸润、免疫治疗和药物敏感性方面表现出显著差异。

讨论：衰老特征标志物是 ccRCC 分子分型的实用生物标志物和预测因子。不同亚组之间预后水平、临床分期和分级、免疫浸润、免疫治疗和药物敏感性的差异表明，这种方法可以为 ccRCC 提供有价值的关于衰老相关治疗选择和预后评估的见解。通过生物学实验验证了基因 DUSP1 在 ccRCC 中的功能，证实了其作为 ccRCC 新型生物标志物的可行性。这些发现表明，基于衰老相关机制的靶向治疗可能是 ccRCC 的一种有效治疗选择。