多队列验证:透明细胞肾细胞癌预后标志物的综合研究。
Multi-cohort validation: A comprehensive exploration of prognostic marker in clear cell renal cell carcinoma.
机构信息
Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
出版信息
Int Immunopharmacol. 2024 Jun 30;135:112300. doi: 10.1016/j.intimp.2024.112300. Epub 2024 May 22.
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.
透明细胞肾细胞癌(ccRCC)是 RCC 中最常见的形式。它的特点是对传统放疗和化疗具有抗性,以及临床预后不良。虽然 TYMP 参与了肿瘤进展,但 TYMP 在 ccRCC 中的作用仍不清楚。通过数据库挖掘发现 TYMP 在 ccRCC 中表达升高,并在 RCC 细胞系中得到证实。事实上,TYMP 敲低会影响 RCC 细胞的体外增殖、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,TCGA-ccRCC 和外部队列中 TYMP 高表达的患者预后不良。单细胞分析的结果表明,TYMP 的分布主要在单核细胞和巨噬细胞中观察到。此外,TYMP 与免疫状态之间存在显著关联。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,突变分析表明 TYMP 与 ccRCC 驱动基因如 BAP1 和 ROS1 之间存在关联。总之,TYMP 可能是 ccRCC 的可靠预后指标。