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We analyzed single-cell transcriptome data from 73 multi-region samples in 21 pancreatic ductal adenocarcinoma (PDAC) patients to evaluate lncRNAs associated with intra-tumoral heterogeneity and the tumor microenvironment (TME) in PDAC. We found cell-specific lncRNAs that reflected tumor, immune and stromal cell contributions, associated with outcomes, and validated across orthogonal datasets. Single-cell analysis of tumor cells revealed lncRNAs associated with TP53 mutations and FOLFIRINOX treatment that were obscured in bulk tumor analysis. Lastly, we identified tumor cell subclusters revealing lncRNAs associated with processes such as epithelial-mesenchymal transition (EMT) signaling. These subclusters, which were validated across six datasets, showed clinically relevant associations with patient outcomes that were independent of clinico-pathologic features. We hope that this database of PDAC lncRNAs can serve as a resource to guide future functional studies.

Outline of Analysis 

PDAC lncRNA graphical abstract.png
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