Department of Urology, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
School of Life Sciences, Jiangsu Normal University, Jiangsu, China.
Clin Transl Med. 2023 Jul;13(7):e1338. doi: 10.1002/ctm2.1338.
Recurrent bladder cancer is the most common type of urinary tract malignancy; nevertheless, the mechanistic basis for its recurrence is uncertain. Innovative technologies such as single-cell transcriptomics and spatial transcriptomics (ST) offer new avenues for studying recurrent tumour progression at the single-cell level while preserving spatial data.
This study integrated single-cell RNA (scRNA) sequencing and ST profiling to examine the tumour microenvironment (TME) of six bladder cancer tissues (three from primary tumours and three from recurrent tumours).
scRNA data-based ST deconvolution analysis revealed a much higher tumour heterogeneity along with TME in recurrent tumours than in primary tumours. High-resolution ST analysis further identified that while the overall natural killer/T cell and malignant cell count or the ratio of total cells was similar or even lower in the recurrent tumours, a higher interaction between epithelial and immune cells was detected. Moreover, the analysis of spatial communication reveals a marked increase in activity between cancer-associated fibroblasts (CAFs) and malignant cells, as well as other immune cells in recurrent tumours.
We observed an enhanced interplay between CAFs and malignant cells in bladder recurrent tumours. These findings were first observed at the spatial level.
复发性膀胱癌是最常见的尿路恶性肿瘤类型；然而，其复发的机制基础尚不确定。单细胞转录组学和空间转录组学（ST）等创新技术为在保留空间数据的情况下在单细胞水平上研究复发性肿瘤进展提供了新的途径。
本研究整合了单细胞 RNA（scRNA）测序和 ST 分析，以检查 6 个膀胱癌组织（3 个来自原发性肿瘤，3 个来自复发性肿瘤）的肿瘤微环境（TME）。
基于 scRNA 数据的 ST 反卷积分析显示，复发性肿瘤中的肿瘤异质性以及 TME 明显高于原发性肿瘤。高分辨率 ST 分析进一步表明，尽管复发性肿瘤中的总自然杀伤/T 细胞和恶性细胞计数或总细胞的比例相似甚至更低，但上皮细胞和免疫细胞之间的相互作用更高。此外，空间通讯分析表明，复发性肿瘤中癌症相关成纤维细胞（CAF）与恶性细胞以及其他免疫细胞之间的活性显著增加。
我们观察到膀胱癌复发性肿瘤中 CAF 与恶性细胞之间的相互作用增强。这些发现首先在空间水平上观察到。
