多队列验证:透明细胞肾细胞癌预后标志物的综合探索。
Multi-cohort validation: A comprehensive exploration of prognostic marker in clear cell renal cell carcinoma.
发表日期:2024 May 22
作者:
Yifei Li, Congcong Fan, Yuhang Hu, Weizhi Zhang, Hang Li, Yining Wang, Ziqiang Xu
来源:
GENES & DEVELOPMENT
摘要:
透明细胞肾细胞癌 (ccRCC) 是最常见的 RCC 形式。其特点是对传统放疗和化疗产生耐药性,临床预后不良。尽管 TYMP 与肿瘤进展有关,但 TYMP 在 ccRCC 中的作用仍不清楚。通过数据库挖掘在 ccRCC 中鉴定出 TYMP 表达升高,并在 RCC 细胞系中得到证实。事实上,TYMP 敲低会影响体外肾细胞癌细胞的增殖、迁移和侵袭。 TYMP与临床病理参数(组织学分级、病理分期)呈正相关。此外,在 TCGA-ccRCC 和外部队列中,TYMP 高表达的患者表明预后不良。单细胞分析结果表明,TYMP主要分布在单核细胞和巨噬细胞中。此外,TYMP 与免疫状态之间存在显着关联。甲基化分析进一步阐明了TYMP表达与多个甲基化位点之间的关系。药物敏感性分析揭示了潜在的药物选择。此外,突变分析还确定了 TYMP 与 BAP1 和 ROS1 等 ccRCC 驱动基因之间的关联。总之,TYMP 可作为 ccRCC 的可靠预后指标。版权所有 © 2024 Elsevier B.V. 保留所有权利。
Clear cell renal cell carcinoma (ccRCC) is the most common form of RCC. It is characterized by resistance to traditional radiotherapy and chemotherapy, as well as an unfavorable clinical prognosis. Although TYMP is implicated in the advancement of tumor progression, the role of TYMP in ccRCC is still not understood. Heightened TYMP expression was identified in ccRCC through database mining and confirmed in RCC cell lines. Indeed, TYMP knockdown impacted RCC cell proliferation, migration, and invasion in vitro. TYMP showed a positive correlation with clinicopathological parameters (histological grade, pathological stage). Moreover, patients with high TYMP expression were indicative of poor prognosis in TCGA-ccRCC and external cohorts. The results of single-cell analysis showed that the distribution of TYMP was predominantly observed in monocytes and macrophages. Furthermore, there is a significant association between TYMP and immune status. Methylation analysis further elucidated the relationship between TYMP expression and multiple methylation sites. Drug sensitivity analysis unveiled potential pharmaceutical options. Additionally, mutation analyses identified an association between TYMP and the ccRCC driver genes like BAP1 and ROS1. In summary, TYMP may serve as a reliable prognostic indicator for ccRCC.Copyright © 2024 Elsevier B.V. All rights reserved.