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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (1): 21-29.doi: 10.3969/j.issn.1674-5671.2025.01.03

• 基础研究 • 上一篇    下一篇

基于组学技术分析lncRNA MBNL1⁃AS1 对Basal 型肌层浸润性膀胱癌的分子特征影响

  

  1. 广西医科大学第一附属医院检验科；广西医科大学基因组与个体化医学研究中心；广西医科大学附属肿瘤医院泌尿外科；广西医科大学第一附属医院肝胆外科；南宁市第六人民医院泌尿外科；广西医科大学第一附属医院泌尿外科；广西医科大学附属肿瘤医院内科
  • 出版日期:2025-02-25 发布日期:2025-03-06
  • 通讯作者: 汤绍梅， E-mail：544673765@qq.com；王秋雁， E-mail：wangqiuyan@gxmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（82160501）；广西科技基地和人才专项（桂科AD22035042）；广西壮族自治区卫生健康委员会自筹经费科研课题（Z20190664）

Analyzing the impact of lncRNA MBNL1-AS1 on the molecular characteristics of Basal subtype muscle-invasive bladder cancer based on omics technologies

  • Online:2025-02-25 Published:2025-03-06

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摘要： 目的 探究肌层浸润性膀胱癌（muscle⁃invasive bladder cancer，MIBC）分子亚型特异性，为不同MIBC分子亚型患者的治疗提供指导。方法 基于MIBC分子分型方法中的UNC分型法，应用转录组测序数据，将48例MIBC患者分为2种分子亚型即Basal型和Luminal型，并进行差异表达分析以探究MIBC特异性的lncRNAs，并进一步探讨其分子特征和临床意义。结合单细胞质谱流式细胞术（single⁃cell mass cytometry，CyTOF）和镜像质谱流式细胞术（imaging mass cytometry，IMC）分析MBNL1⁃AS1高表达组和低表达组Basal型MIBC患者的免疫微环境异质性。结果 基于分子分型法筛选发现了在MIBC特异性表达的lncRNA MBNL1⁃AS1，其低表达与Basal型MIBC患者的不良预后密切相关（P=0.022）。且进一步分析转录组测序数据后发现，在Basal型MIBC中，MBNL1⁃AS1低表达组具有去分化（P=0.008）、高干性（P=0.020）和高增殖（P=0.010）的特征。MBNL1⁃AS1低表达组的Basal型MIBC患者的免疫评分与NK CD56bright细胞和Treg细胞的评分呈负相关（P<0.05），而MBNL1⁃AS1高表达组的B细胞和CD8+T细胞相关基因的表达水平较高。高维度单细胞蛋白质组学分析结果显示，MBNL1⁃AS1低表达的Basal型MIBC患者表现出较高的Treg细胞亚群丰度（P=0.016）。结论 MBNL1⁃AS1低表达组的Basal型MIBC患者具有去分化、高干性、高增殖和免疫抑制的特点。MBNL1⁃AS1具有作为Basal型MIBC免疫响应生物标志物的潜能。

关键词: Basal型肌层浸润性膀胱癌, MBNL1?AS1, 肿瘤免疫微环境

Abstract: Objective To investigate the molecular subtype specificity of muscle⁃invasive bladder cancer (MIBC) and provide therapeutic guidance for patients with different MIBC molecular subtypes. Methods Based on the UNC molecular typing method for MIBC, transcriptome sequencing data from 48 MIBC patients were used to classify them into two molecular subtypes: Basal and Luminal. Differential expression analysis was performed to explore MIBC⁃specific lncRNAs, followed by further investigation of their molecular characteristics and clinical significance. Combining single⁃cell mass cytometry (CyTOF) and imaging mass cytometry (IMC), the immune microenvironment heterogeneity of Basal subtype MIBC patients with high and low MBNL1⁃AS1 expression was analyzed. Results Molecular subtyping analysis revealed that lncRNA MBNL1⁃AS1 is specifically expressed in MIBC, and its low expression was significantly associated with poor prognosis in the Basal subtype MIBC patients (P=0.022). Further analysis of transcriptome sequencing data revealed that the MBNL1⁃AS1 low expression group in Basal subtype MIBC exhibited characteristics of dedifferentiation (P=0.008), elevated stemness (P=0.020), and high proliferation (P=0.010). The immune score of Basal MIBC patients with low MBNL1⁃AS1 expression showed a significant negative correlation with NK CD56bright cells and Treg cells (P<0.05), while the expression levels of B cell⁃ and CD8+ T cell⁃related genes were elevated in the high MBNL1⁃AS1 expression group. High⁃dimensional single⁃cell proteomics analysis revealed that Basal MIBC patients with low MBNL1⁃AS1 expression exhibited a higher abundance of Treg cells (P=0.016).  Conclusions Basal MIBC patients in the low MBNL1⁃AS1 expression group demonstrated the characteristics of dedifferentiation, elevated stemness, high proliferation, and immune suppression. MBNL1⁃AS1 has the potential to serve as a biomarker for predicting immune response in Basal MIBC. 

Key words: Basal muscle?invasive bladder cancer, MBNL1?AS1, Tumor immune microenvironment

中图分类号: 

  • R737.14