基于单细胞RNA测序与TCGA数据整合的 膀胱癌基质细胞核心亚群分析及分子分型

Analysis of Core Stromal Cell Subpopulations and Molecular Subtyping in Bladder Cancer Based on Integration of Single-Cell RNA Sequencing and TCGA Data

摘要: 本研究旨在系统解析膀胱癌组织中基质细胞的异质性，探索其与正常组织的差异，并评估其在患者分型及预后中的潜在价值。利用从基因表达综合(GEO)数据库获取的单细胞RNA测序(scRNA-seq)数据，系统解析了膀胱癌组织与正常膀胱组织间的差异，并基于所鉴定的细胞亚群，通过样本一致性聚类方法对TCGA患者的膀胱癌样本进行了分型研究，批量RNA-seq数据来源于TCGA数据库。结果发现，与正常组织相比，膀胱癌组织中的成纤维细胞数量显著减少；膀胱癌组织中的成纤维细胞亚群高表达ECM受体相互作用通路相关基因，而内皮细胞亚群则高表达包括DLL4和NOTCH4在内的NOTCH信号通路基因。基于细胞亚群评分，我们将TCGA膀胱癌患者分为三种亚型，其中G3亚型的亚群评分最低且预后最佳。综上所述，膀胱癌组织中的成纤维细胞和内皮细胞亚群可能促进肿瘤发生，为进一步探索膀胱癌的具体机制提供了理论基础；同时，通过对TCGA膀胱癌患者进行分子分型，本研究可能为膀胱癌的分期诊断提供新思路。这些结果增进了对膀胱尿路上皮癌患者间异质性的理解，并为个体化治疗奠定了基础。

Abstract: This study aimed to systematically characterize the heterogeneity of stromal cells in bladder cancer tissues, explore their differences from normal tissues, and evaluate their potential value in patient subtyping and prognosis. Using single-cell RNA sequencing (scRNA‑seq) data obtained from the Gene Expression Omnibus (GEO) database, we systematically analyzed the differences between bladder cancer tissues and normal bladder tissues. Based on the identified cell subpopulations, we performed consensus clustering to classify bladder cancer samples from TCGA patients, with bulk RNA‑seq data obtained from the TCGA database. The results showed that, compared with normal tissues, the number of fibroblasts was significantly reduced in bladder cancer tissues. Fibroblast subpopulations in bladder cancer tissues highly expressed genes related to the ECM‑receptor interaction pathway, while endothelial subpopulations highly expressed NOTCH signaling pathway genes including DLL4 and NOTCH4. Based on cell subpopulation scores, we classified TCGA bladder cancer patients into three subtypes, among which the G3 subtype had the lowest subpopulation score and the best prognosis. In conclusion, fibroblast and endothelial cell subpopulations in bladder cancer tissues may promote tumorigenesis, providing a theoretical basis for further exploration of the specific mechanisms underlying bladder cancer. Furthermore, the molecular subtyping of TCGA bladder cancer patients in this study may offer new insights for staging diagnosis of bladder cancer. These findings enhance our understanding of interpatient heterogeneity in bladder urothelial carcinoma and lay a foundation for personalized treatment.