Gene expression of matched treatment-naive versus FOLFIRINOX-treated PDAC patient-derived organoids
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ABSTRACT:
PROVIDER: PRJNA796009 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17534466_1.fastq.gz | Fastqsanger.gz | |||
| SRR17534466_2.fastq.gz | Fastqsanger.gz | |||
| SRR17534467_1.fastq.gz | Fastqsanger.gz | |||
| SRR17534467_2.fastq.gz | Fastqsanger.gz | |||
| SRR17534468_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2022-03-09 | GSE193389 | GEO
Project description:Pancreatic ductal adenocarcinoma is an extreme lethal cancer with a poor treatment response to all the current chemotherapies. We generated a library of PDAC organoid lines from resected tumors, five from treatment-naive patients and five from patients who received neoadjuvant FOLFIRINOX (eight cycles). We assessed weather residual cancer cells in the tumor lesions of the patients treated with neoadjuvant FOLFIRINOX developed resistance to the treatment. Further we perfromed transcriptome analysis to investigate: 1- weather organoids recapitualting their corresponding tumor tissue 2- To investigate any modifications in the expression of the genes inflicted by FOLFIRINOX treatment.
2021-03-23 | GSE169321 | GEO
Project description:The pancreatic cancer tumor microenvironment is dominated primarily by cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). The interecellular dialogue between CAFs and TAMs and the resulting impact on chemoresistance, specifically to Folfirinox, remains poorly understood. In this study, we sought to understand the impact of primary PDAC CAFs on macrophage reprogramming in a folfirinox-dependent manner and performed various cellular assays (viability, immunophenotyping, phagocytosis, secretory profile analysis) and transcriptomic analysis.
2024-01-10 | GSE226448 | GEO
Project description:Purpose: FOLFIRINOX has become standard therapy for patients with advanced stages pancreatic ductal adenocarcinoma (PDAC). However, only a subset of patients benefits from this therapy and biomarkers to guide clinical decisions are lacking. This study aimed to discover circulating microRNAs (miRNAs) as potential stratifying and monitoring biomarkers in patients with PDAC treated with FOLFIRINOX and to investigate their functional roles. Methods: A microarray was used in plasma samples from a first cohort of 11 patients selected based on their long versus short progression-free survival (PFS) after FOLFIRINOX. Nine miRNAs were validated using RT-qPCR in an independent cohort (n=43). The best discriminative miRNA was evaluated in tumor tissue samples and associated with clinicopathological features by Cox regression analyses. In vitro studies explored its role on cell proliferation, key downstream targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: MiR-181a-5p was validated as significantly down-regulated in non-progressive compared to progressive patients after FOLFIRINOX. In multivariate analysis, this down-regulation correlated with improved PFS and overall survival, especially combined with CA19.9 decline (log-rank p<0.001, HR=0.153, 95% C.I. 0.067–0.347 and log-rank p=0.033, HR=0.201, 95% C.I. 0.070–0.576, respectively). Overexpression of miR-181a-5p increased proliferation of PDAC cells and inversely correlated with expression of ATM. Furthermore, inhibition of miR-181a-5p coupled with oxaliplatin exposure increased DNA damage and decreased cell viability. Conclusion: Our findings endorse miR-181a-5p as a biomarker for monitoring response to FOLFIRINOX and prognostication. MiR-181a-5p inhibition can potentially enhance sensitivity to oxaliplatin by amplifying the DNA damage response and cell death.
2019-01-01 | GSE109647 | GEO
Project description:To determine the lncRNA and mRNA expression profile in PDAC and matched non-tumor tissues, we uesed lncRNA microArray analysis form Arraystar to examine the expression of lncRNAs and mRNAs in PDAC and matched non-tumor tissues.
2017-07-11 | GSE101094 | GEO
Project description:We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance.
| EGAS00001006661 | EGA
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived tumor xenografts (PDTXs) have been increasingly used as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. Extensive multiomics characterization of these PDTXs have demonstrated their utility as a suitable model for preclinical studies, representing the diversity of the primary cancers. We performed a multi-factorial integrative analysis of genome-wide ChIP-seq on multiple histone modifications, as well as RNA-seq on subcutaneous PDTXs from 24 PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). In the dataset, ChIP-seq for five distinct histone marks (H3K4me1, H3K27ac, H3K4me3, H3K27me3, and H3K9me3) and RNA-seq was carried out to generate new knowledge on the epigenetic landscapes underlying the heterogeneity of PDAC tissues grown in this manner.
2018-05-29 | E-MTAB-5632 | biostudies-arrayexpress
Project description:The presence of some malignancies, such as cancer, impacts on peripheral blood mononuclear cells (PBMCs) gene expression profiling, suggesting the potential suitability of these genes as diagnostic and prognostic markers. The objective of this study was to identify new markers in peripheral blood that differentiate between PDAC patients and healthy controls as a means of facilitating early detection of the disease. 18 patients with unresectable PDAC were recruited. The diagnosis of PDAC was based on a positive biopsy of the pancreatic mass during the surgery. 18 gender, age, and habits matched healthy controls were also included. Whole genome cDNA microarray hybridization of PBMC samples was performed to identify potential PDAC markers.
2013-08-12 | E-GEOD-49641 | biostudies-arrayexpress
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived tumor xenografts (PDTXs) have been increasingly used as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. Extensive multiomics characterization of these PDTXs have demonstrated their utility as a suitable model for preclinical studies, representing the diversity of the primary cancers. We performed a multi-factorial integrative analysis of genome-wide ChIP-seq on multiple histone modifications, as well as RNA-seq on subcutaneous PDTXs from 24 PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). In the dataset, ChIP-seq for five distinct histone marks (H3K4me1, H3K27ac, H3K4me3, H3K27me3, and H3K9me3) and RNA-seq was carried out to generate new knowledge on the epigenetic landscapes underlying the heterogeneity of PDAC tissues grown in this manner. <br>Note: Sample phenotypes have been updated on 2020-09-11 to correct the swapped labels between \"classical\" and \"basal\" phenotypes.
2018-05-29 | E-MTAB-5639 | biostudies-arrayexpress
Project description:Patient-derived organoids after neoadjuvant FOLFIRINOX predict therapy resistance in pancreatic ductal adenocarcinoma
| PRJNA716264 | ENA