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Series GSE171351 Query DataSets for GSE171351
Status Public on Jun 04, 2021
Title A new epithelial cell subpopulation predicts response to surgery, chemotherapy, and immunotherapy in bladder cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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-naïve muscle-invasive bladder cancer (n=4) fresh-frozen tissue.
 
Contributor(s) Gouin III KH, Ing N, Knott SR, Theodorescu D
Citation(s) 34385456, 37344596
Submission date Apr 01, 2021
Last update date Apr 05, 2024
Contact name Kenneth Howard Gouin III
E-mail(s) Kgouiniii@gmail.com
Organization name Cedars-Sinai Medical Center
Street address 8700 Beverly Blvd
City Los Angeles
State/province CA
ZIP/Postal code 90048
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (4)
GSM5224027 MIBC_B1204
GSM5224028 MIBC_B8
GSM5224029 MIBC_B72
Relations
BioProject PRJNA719160
SRA SRP313147

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Supplementary file Size Download File type/resource
GSE171351_RAW.tar 68.3 Mb (http)(custom) TAR (of JPG)
GSE171351_combined_visium.h5ad.gz 46.7 Mb (ftp)(http) H5AD
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Raw data are available in SRA
Processed data are available on Series record

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