Integrated single‐cell and spatial transcriptomic profiling reveals higher intratumour heterogeneity and epithelial–fibroblast interactions in recurrent bladder cancer

Author:

Shi Zhen‐Duo1234,Sun Zhuo5,Zhu Zuo‐Bin6,Liu Xing1,Chen Jun‐Zhi1,Hao Lin1,Zhu Jie‐Fei7,Pang Kun1,Wu Di7,Dong Yang1,Liu Yu‐Fei8,Chen Wei‐Hua9,Liang Qing1,Zhuo Shi‐Chao7,Han Cong‐Hui123ORCID

Affiliation:

1. Department of Urology Xuzhou Clinical School of Xuzhou Medical University Xuzhou Central Hospital Xuzhou Jiangsu China

2. School of Life Sciences Jiangsu Normal University Jiangsu China

3. Department of Urology Heilongjiang Provincial Hospital Heilongjiang China

4. Department of Urology Peixian People's Hospital Jiangsu China

5. Department of Pathology, Laboratory of Clinical and Experimental Pathology Xuzhou Medical University Xuzhou Jiangsu China

6. Department of Genetics Xuzhou Engineering Research Center of Medical Genetics and Transformation, Key Laboratory of Genetic Foundation and Clinical Application Xuzhou Medical University Xuzhou China

7. Department of Pathology Xuzhou Central Hospital Xuzhou Jiangsu China

8. Department of Urology Huashan Hospital Fudan University Shanghai China

9. Department of Urology Shanghai East Hospital, Tongji University School of Medicine Shanghai China

Abstract

AbstractBackgroundRecurrent 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.MethodThis 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).FindingsscRNA 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.InterpretationWe observed an enhanced interplay between CAFs and malignant cells in bladder recurrent tumours. These findings were first observed at the spatial level.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Molecular Medicine,Medicine (miscellaneous)

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