A new epithelial cell subpopulation predicts response to surgery, chemotherapy, and immunotherapy in bladder cancer
Dataset ID: STDS0000067
4,086 Spots
33,538 Genes


Dataset information
The advent of neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management1-7. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single cell resolution spatial proteomic analysis of human bladder cancer to identify a novel epithelial subpopulation with therapeutic response prediction ability. These cells were defined by expression of Cadherin 12 (CDH12, N-Cadherin 2), catenins and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors had a superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offered better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherent chemoresistance mediated through ALDH1A1 expression and fibroblast activation potential. Furthermore, CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a new cancer cell population with an intriguing diametric response to the major therapeutic modalities in bladder cancer. Importantly, it also provides a compelling rationale for the design of novel biomarker guided therapeutic clinical trials.
Overall design
Visium spatial transcriptomics of human treatment-na茂ve muscle-invasive bladder cancer (n=4) fresh-frozen tissue.
10x Visium
Illumina NovaSeq 6000
Homo sapiens
Muscle-invasive bladder cancer
Bladder cancer
Gouin KH 3rd, Ing N, Plummer JT, Rosser CJ et al. An N-Cadherin 2 expressing epithelial cell subpopulation predicts response to surgery, chemotherapy and immunotherapy in bladder cancer. Nat Commun 2021 Aug 12;12(1):4906
Submission date: 2021-04-01Update date: 2021-08-24
Sample number: 4

Kenneth H Gouin III; Nathan Ing; Simon R Knott; Dan Theodorescu

GEO Series Accessions: GSE171351
snSeq GEO Series Accessions: GSE169379