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Status |
Public on Jun 30, 2021 |
Title |
Transcriptomic Analysis of Laser Capture Microdissected Tumors of Pancreatic Ductal Adenocarcinoma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
In this study, we performed laser capture microdissection (LCM) of PDAC samples to define their cancer- and stroma-specific molecular subtypes and identify a prognostic gene expression signature for short-term and long-term survival. LCM and RNA-seq analysis of cancer and adjacent stroma of 19 treatment-naïve PDAC tumors were performed. Gene expression signatures were tested for their robustness in a large independent validation set. An RNA in situ hybridization (RNA-ISH) assay with pooled probes for genes associated with disease-free survival (DFS) was developed to probe 111 PDAC tumor samples. Gene expression profiling identified four subtypes of cancer cells (C1-C4) and three subtypes of cancer-adjacent stroma (S1-S3). These stroma-specific subtypes were associated with DFS (p=5.55E-07), with S1 associated with better prognoses when paired with C1 and C2. Thirteen genes were found to be predominantly expressed in cancer cells and corresponded with DFS in a validation using existing RNA-seq datasets. A second validation on an independent cohort of patients using RNA-ISH probes to six of these prognostic genes demonstrated significant association with overall survival (median 17 versus 25 months; p<0.02). Our results identified specific signatures from the epithelial and the stroma components of PDAC, which add clarity to the nature of PDAC molecular subtypes and may help predict survival.
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Overall design |
Gene expression analysis of cancer cells and adjacent (<280 μm) stromal cells
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Contributor(s) |
Birnbaum DJ, Begg SK, Finetti P, Vanderburg C, Kulkarni AS, Neyaz A, Hank T, Tai E, Deshpande V, Bertucci F, Birnbaum D, Lillemoe KD, Warshaw AL, Mino-Kenudson M, Fernandez-Del Castillo C, Ting DT, Liss AS |
Citation(s) |
33547202 |
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Submission date |
Jan 12, 2021 |
Last update date |
Dec 21, 2023 |
Contact name |
Andrew S Liss |
Organization name |
Massachusetts General Hospital
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Department |
Surgery
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Lab |
Liss Laboratory
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Street address |
55 Blossom St
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02114 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (38)
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Relations |
BioProject |
PRJNA691527 |
SRA |
SRP301415 |
Supplementary file |
Size |
Download |
File type/resource |
GSE164665_Cancer_raw_gene_counts.txt.gz |
726.3 Kb |
(ftp)(http) |
TXT |
GSE164665_Stroma_raw_gene_counts.txt.gz |
664.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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