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Status |
Public on Sep 22, 2022 |
Title |
Single-cell RNA Sequencing Demonstrates Inter-Patient Heterogeneity and Altered Tumor Microenvironment in Invasive and Intraductal Cribriform Prostate Cancer |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
ICC and IDC are aggressive histological subtypes of prostate cancer that are associated with progression to lethal disease. To delineate cancer cell intrinsic as well as tumor microenvironmental factors that contribute to ICC/IDC aggressiveness, this study examined paired ICC/IDC-enriched and benign-enriched prostate samples obtained from radical prostatectomy (RP) by scRNAseq, TCR sequencing and histology. ICC/IDC cancer cells had robust inter-patient heterogeneity but upregulated similar pathways (MYC and TNF via NFĸB) and targets with potential for therapeutic intervention (PSMA and B7-H3). ICC/IDC was associated with increased neovasculature, and cancer foci were densely circumscribed by immunosuppressive CAF likely derived from APOD+ peri-epithelial fibroblast progenitors. The ICC/IDC TME had fewer and more dysfunctional T cells and increased M2 polarization of two macrophage subtypes compared to benign prostate. These findings support that ICC/IDC are hallmarked by several aggressive features that likely contribute to their association with lethal prostate cancer.
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Overall design |
scRNA-seq (whole transcriptome and TCR) performed on paired ICC/IDC-enriched and benign-enriched prostate samples obtained from radical prostatectomy.
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Contributor(s) |
Hurley PJ, Wong H, Sheng Q |
Citation(s) |
36229464 |
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Submission date |
Oct 05, 2021 |
Last update date |
Oct 28, 2022 |
Contact name |
Hong Yuen Wong |
Organization name |
VUMC
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Department |
Medicine
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Lab |
Hurley Lab
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Street address |
2220 Pierce Ave # PRB648, Preston Research Building
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City |
Nashville |
State/province |
Tennessee |
ZIP/Postal code |
37232 |
Country |
USA |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (21)
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Relations |
BioProject |
PRJNA768795 |
SRA |
SRP340106 |