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GEO help: Mouse over screen elements for information. |
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Status |
Public on May 12, 2022 |
Title |
Spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here we construct a high-resolution molecular landscape of the multicellular subtypes and spatial communities that compose PAC using single-nucleus RNA-seq and whole-transcriptome digital spatial profiling (SP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment-naïve. We uncovered expression programs across malignant cells and fibroblasts, including a newly-identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities: classical, squamoid-basaloid, and treatment-enriched. Our refined molecular and cellular taxonomy can advance precision oncology in PAC through stratification in clinical trials and as roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.
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Overall design |
14 specimens received no treatment prior to resection; 7 specimens received neoadjuvant chemotherapy, radiotherapy, losartan, and/or nivolumab prior to resection
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Contributor(s) |
Hwang WL, Jagadeesh KA, Guo JA, Hoffman HI, Su J, Shiau C, Jacks T, Regev A |
Citation(s) |
35902743 |
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Submission date |
Mar 21, 2022 |
Last update date |
Sep 11, 2023 |
Contact name |
Karthik Jagadeesh |
E-mail(s) |
kjag@broadinstitute.org
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Phone |
4088919573
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Organization name |
Broad Institute
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Department |
Human Cell Atlas
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Lab |
Regev Lab
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Street address |
415 Main St
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (608)
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Relations |
BioProject |
PRJNA818705 |
Supplementary file |
Size |
Download |
File type/resource |
GSE199102_Broad_PDAC_WTA_AllSamples_SegmentProperties.txt.gz |
68.6 Kb |
(ftp)(http) |
TXT |
GSE199102_RAW.tar |
32.7 Mb |
(http)(custom) |
TAR (of DCC) |
GSE199102_dfs_Q321-6.RDS.gz |
22.9 Mb |
(ftp)(http) |
RDS |
GSE199102_dfs_detrendApproach21-6-2.RDS.gz |
34.6 Mb |
(ftp)(http) |
RDS |
GSE199102_geomx_ngs_data_second_acquisition_WTA_Hs_R_NGS_WTA_v1.0.pkc.gz |
1.9 Mb |
(ftp)(http) |
PKC |
GSE199102_hPDAC_WTA_20210222T2101_BioProbeCountMatrix.txt.gz |
9.3 Mb |
(ftp)(http) |
TXT |
GSE199102_hPDAC_WTA_20210222T2101_LabWorksheet.txt.gz |
7.9 Kb |
(ftp)(http) |
TXT |
GSE199102_hPDAC_WTA_20210222T2101_NegNorm_TargetCountMatrix.txt.gz |
61.6 Mb |
(ftp)(http) |
TXT |
GSE199102_hPDAC_WTA_20210222T2101_Q3Norm_TargetCountMatrix.txt.gz |
22.3 Mb |
(ftp)(http) |
TXT |
GSE199102_hPDAC_WTA_20210222T2101_TargetCountMatrix.txt.gz |
8.9 Mb |
(ftp)(http) |
TXT |
GSE199102_ssGSEA_detrendApproach21-6-2.RDS.gz |
228.4 Kb |
(ftp)(http) |
RDS |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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