Transcriptomics

Dataset Information

0

Gene expression of matched treatment-naive versus FOLFIRINOX-treated PDAC patient-derived organoids


ABSTRACT: In our study, we aimed to investigate adaptive processes of tumors under treatment and therefore, generated PDAC patient-derived organoids (PDOs) and 2D cell lines before and after chemotherapy. We enrolled a patient with borderline resectable PDAC who received neoadjuvant FOLFIRINOX. Endoscopic fine needle (pre-FFX) and surgical biopsies (post-FFX) were used to generate PDOs and 2D cells. Whole exome sequencing (WES) and RNA sequencing data of the pre-FFX and post-FFX organoids were compared in order to evaluate the genetic landscape and PDAC subtypes. Although transcriptional subtyping classified both PDOs as classical PDAC, gene set enrichment analysis (GSEA) revealed a reduced pathway activation linked to the basal-like phenotype such as KRAS signaling in the post-FFX organoids. WES did not show major differences in the genetic landscape of the tumor pre- and post-FFX induction suggesting a plasticity process rather than a clonal selection during chemotherapy. 2D cells were subjected to an unbiased automated drug screening of 415 compounds to investigate FFX-induced vulnerabilities. Top targets such as MEK inhibitors were validated manually in the 2D cells and organoids and an increased sensitivity was observed in the post-FFX cells. Thus, integrating functional layers into personalized medicine allows to identify chemotherapy-induced vulnerabilities as potent targeted therapy options in PDAC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193389 | GEO | 2022/03/09

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2021-08-07 | GSE181593 | GEO
2022-04-28 | GSE173339 | GEO
2024-11-03 | GSE280749 | GEO
2024-04-11 | GSE228801 | GEO
2022-10-12 | GSE212014 | GEO
2022-05-19 | PXD023424 | Pride
| PRJNA814344 | ENA
2023-01-09 | GSE205013 | GEO
2023-12-06 | GSE239386 | GEO
2020-06-16 | GSE141737 | GEO