Ning Wei, Yang Yan-Ru, Wu Chen-Xu, Hou Yue, Liu Zhi-Wei, Yang Chang-Bin
Medical Innovation Center, Air Force Medical University, Xi'an, China.
Department of Pathology, the First Affiliated Hospital of Air Force Medical University, Xi'an, China.
Front Oncol. 2025 Jun 24;15:1564826. doi: 10.3389/fonc.2025.1564826. eCollection 2025.
Bladder cancer (BLCA) is a prevalent and aggressive disease characterized by substantial molecular heterogeneity, complicating its diagnosis and treatment. Existing therapies, including surgery and chemotherapy, often lack specificity. Alterations in cell death mechanisms, such as ferroptosis, cuproptosis, and immunogenic cell death, significantly impact cancer progression and prognosis.
We analyzed gene expression data from TCGA and GEO. Cox regression analyses generated a prognostic risk score model incorporating LIPT1, ACSL5, and CHMP6. This model successfully stratified BLCA patients into different risk categories and was validated through survival analysis, immune infiltration, mutation burden assessment, drug sensitivity predictions, and single-cell analysis. The high-risk group was linked to differentiation processes, developmental stages, and active metabolic pathways.
Experimental validation highlighted CHMP6's role in enhancing BLCA cell survival and migration by regulating the cell cycle. The model's prognostic relevance was further supported by drug sensitivity and immune metrics. These results provide valuable insights into potential biomarkers and therapeutic targets for BLCA treatment.
The CHMP6 protein promotes BLCA cell survival and invasive migration through modulation of the cell cycle.
膀胱癌(BLCA)是一种常见且侵袭性强的疾病,其特征是存在大量分子异质性,这使其诊断和治疗变得复杂。包括手术和化疗在内的现有疗法往往缺乏特异性。细胞死亡机制的改变,如铁死亡、铜死亡和免疫原性细胞死亡,会显著影响癌症的进展和预后。
我们分析了来自TCGA和GEO的基因表达数据。Cox回归分析生成了一个包含LIPT1、ACSL5和CHMP6的预后风险评分模型。该模型成功地将BLCA患者分为不同的风险类别,并通过生存分析、免疫浸润、突变负担评估、药物敏感性预测和单细胞分析进行了验证。高风险组与分化过程、发育阶段和活跃的代谢途径相关。
实验验证突出了CHMP6通过调节细胞周期在增强BLCA细胞存活和迁移中的作用。药物敏感性和免疫指标进一步支持了该模型的预后相关性。这些结果为BLCA治疗的潜在生物标志物和治疗靶点提供了有价值的见解。
CHMP6蛋白通过调节细胞周期促进BLCA细胞存活和侵袭性迁移。