Background: 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.
Method: 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).
Findings: 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.
Interpretation: We observed an enhanced interplay between CAFs and malignant cells in bladder recurrent tumours. These findings were first observed at the spatial level.
Keywords: bladder cancer; fibroblast cell; single-cell sequencing; spatial transcriptome; tumour recurrence.
© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.