Basal‐like and classical cells coexist in pancreatic cancer revealed by single‐cell analysis on biopsy‐derived pancreatic cancer organoids from the classical subtype

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is composed of stromal, immune, and cancerous epithelial cells. Transcriptomic analysis of the epithelial compartment allows classification into different phenotypic subtypes as classical and basal‐like. However, little is known about the intra‐tumor heterogeneity particularly in the epithelial compartment. Growing evidences suggest that this phenotypic segregation is not so precise and different cancerous cell types may coexist in a single tumor. To test this hypothesis, we performed single‐cell transcriptomic analyses using combinational barcoding exclusively on epithelial cells from six different classical PDAC patients obtained by Endoscopic Ultrasound (EUS) with Fine Needle Aspiration (FNA). To purify the epithelial compartment, PDAC were grown as biopsy‐derived pancreatic cancer organoids. Single‐cell transcriptomic analysis allowed the identification of four main cell clusters present in different proportions in all tumors. Remarkably, although all these tumors were classified as classical, one cluster present in all corresponded to a basal‐like phenotype. These results reveal an unanticipated high heterogeneity of pancreatic cancers and demonstrate that basal‐like cells, which have a highly aggressive phenotype, are more widespread than expected.

Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatment

“…Consistent with recent reports of intra-tumoral subtype heterogeneity, nearly every untreated tumor contained both basal-like and classical-like cells ( Figure S7; Methods) (78,85), with the two states being largely mutually exclusive. In the treated cohort, bulk signatures overlapped in the same nucleus, suggesting that the basal-like and classical-like signatures derived in the treatment-naïve setting may be less relevant in the neoadjuvant treatment context.…”

Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers

“…Among Notch target genes, HES1 and HEY1 expressions were higher in both basal and classical subtypes of PDAC. In contrast, EOGT expression was significantly increased in the basal subtype, which represents a more aggressive phenotype [34]. LFNG expression was not significantly altered ( Figure 1A).…”

Endoscopic Ultrasound-Guided Sampling for Personalized Pancreatic Cancer Treatment

“…Aspiration of core tissue with preserved architecture is also beneficial for diagnosis and obtaining a sufficient amount of sample for the organoid establishment and molecular genetic studies. The success rate of PDO establishment from tissues obtained through EUS-guided sampling is reported to be about 60% to 82% [61,62,[70][71][72][73][74], which is the same success rate as with surgically resected tissues. Furthermore, there is no significant difference in the establishment efficiency between single-pass and double-pass punctures, therefore single-pass punctures with a 22-gauge FNB needle are recommended [74].…”