Chen Zhibin, Chen Dongmao, Song Zhenfeng, Lv Yifan, Qi Defeng
Department of Urology and Andrology, Minimally Invasive Surgery Center, Guangdong Provincial KeyLaboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Front Oncol. 2023 Jan 19;12:1105026. doi: 10.3389/fonc.2022.1105026. eCollection 2022.
Despite substantial advances in the treatment using immune checkpoint inhibitors (ICIs), the clinical expected therapeutic effect on bladder cancer has not been achieved, in which the tumor microenvironment (TME) occupies a notable position. In this research, 10X single-cell RNA-sequencing technology was conducted to analyze seven primary bladder tumor tissues (three non-muscle-invasive bladder cancer (NMIBC) and four muscle-invasive bladder cancer (MIBC)) and seven corresponding normal tissues adjacent to cancer; eight various cell types were identified in the bladder cancer (BC) TME, and a complete TME atlas in bladder cancer was made. Moreover, bladder cancer epithelial cells were further subdivided into 14 subgroups, indicating a high intra-tumoral heterogeneity. Additionally, the differences between NMIBC and MIBC were compared based on differential gene expression heatmap, copy number variation (CNV) distribution heatmap, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network mutual analysis, and the Kaplan-Meier survival prognosis analysis were used to identify six key genes associated with the prognosis of bladder cancer: VEGFA, ANXA1, HSP90B1, PSMA7, PRDX6, and PPP1CB. The dynamic change of the expression distribution of six genes on the pseudo-time axis was further verified by cell pseudo-time analysis.
尽管使用免疫检查点抑制剂（ICI）进行治疗取得了重大进展，但尚未实现对膀胱癌的临床预期治疗效果，其中肿瘤微环境（TME）占据显著地位。在本研究中，采用10X单细胞RNA测序技术分析了7个原发性膀胱肿瘤组织（3个非肌层浸润性膀胱癌（NMIBC）和4个肌层浸润性膀胱癌（MIBC））以及7个相应的癌旁正常组织；在膀胱癌（BC）TME中鉴定出8种不同的细胞类型，并构建了膀胱癌完整的TME图谱。此外，膀胱癌上皮细胞进一步细分为14个亚组，表明肿瘤内异质性较高。此外，基于差异基因表达热图、拷贝数变异（CNV）分布热图、基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）富集分析，比较了NMIBC和MIBC之间的差异。采用加权基因共表达网络分析（WGCNA）、蛋白质-蛋白质相互作用（PPI）网络互作分析和Kaplan-Meier生存预后分析，确定了与膀胱癌预后相关的6个关键基因：VEGFA、ANXA1、HSP90B1、PSMA7、PRDX6和PPP1CB。通过细胞伪时间分析进一步验证了6个基因在伪时间轴上表达分布的动态变化。
