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Series GSE242230 Query DataSets for GSE242230
Status Public on Sep 06, 2023
Title High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n=25). We then combined these samples with surgical resection (n=6) and publicly available samples to increase statistical power (n=80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n=268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.
 
Overall design We performed scRNA-seq of PDAC from standard-of-care time-of-diagnosis endoscopic ultrasound guided fine needle biopsy (EUS-FNB) specimens at the time-of-diagnosis and from surgical samples obtained from tumor resections to enable a clinically integrated, comprehensive view of PDAC
 
Contributor(s) Aadel C, Koushik D
Citation(s) 37857854
Submission date Sep 02, 2023
Last update date Oct 26, 2023
Contact name Erik Storrs
E-mail(s) estorrs@wustl.edu
Organization name Washington University
Street address 660 S Euclid Ave
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (25)
GSM7755911 wu01,scRNA-seq
GSM7755912 wu02,scRNA-seq
GSM7755913 wu03,scRNA-seq
Relations
BioProject PRJNA1012313

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE242230_RAW.tar 444.4 Mb (http)(custom) TAR (of MTX, TSV)
GSE242230_annotations.txt.gz 345.2 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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