|
| Status |
Public on Mar 22, 2023 |
| Title |
Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we have performed snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis.
|
| |
|
| Overall design |
We performed snRNA-seq on 34 samples (25 patients) and matched snATAC-seq on 28 of these samples (24 patients) from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) ccRCC collection.
***RAW data will be deposited at dbGAP***
|
| |
|
| Contributor(s) |
Ding L |
| Citation(s) |
36973268 |
| |
| Submission date |
Mar 21, 2023 |
| Last update date |
Jun 29, 2023 |
| Contact name |
Yige Wu |
| E-mail(s) |
yigewu.app@gmail.com
|
| Phone |
3142950479
|
| Organization name |
Washington University in St. Louis
|
| Department |
Department of Medicine
|
| Street address |
4520 McPherson Ave
|
| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63108 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (62)
|
|
| Relations |
| BioProject |
PRJNA947535 |
Less...
More...