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Patient-derived organoids of pancreatic ductal adenocarcinoma for subtype determination and clinical outcome prediction.
- Source :
-
Journal of gastroenterology [J Gastroenterol] 2024 Jul; Vol. 59 (7), pp. 629-640. Date of Electronic Publication: 2024 Apr 29. - Publication Year :
- 2024
-
Abstract
- Background: Recently, two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the "Classical" and "Basal-like" subtypes, with the former showing better clinical outcomes than the latter. However, the "molecular" classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction.<br />Methods: We utilized tumor samples acquired through endoscopic ultrasound-guided fine-needle biopsy and established a PDO library for subsequent use in morphological assessments, RNA-seq analyses, and in vitro drug response assays. We also conducted a prospective clinical study to evaluate whether analysis using PDOs can predict treatment response and prognosis.<br />Results: PDOs of PDAC were established at a high efficiency (>ā70%) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) and densely proliferating inside (DP type) less than 2 weeks after tissue sampling. RNA-seq analysis revealed that the "morphological" subtype (GL vs. DP) corresponded to the "molecular" subtype ("Classical" vs. "Basal-like"). The "morphological" classification predicted the clinical treatment response and prognosis; the median overall survival of patients with GL type was significantly longer than that with DP type (Pā<ā0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK inhibitor and chloroquine.<br />Conclusions: PDAC PDOs help in subtype determination and clinical outcome prediction, thereby facilitating the bench-to-bedside precision medicine for PDAC.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Male
Prognosis
Female
Aged
Middle Aged
Prospective Studies
Endoscopic Ultrasound-Guided Fine Needle Aspiration methods
Treatment Outcome
Carcinoma, Pancreatic Ductal pathology
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal drug therapy
Organoids pathology
Pancreatic Neoplasms pathology
Pancreatic Neoplasms genetics
Pancreatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1435-5922
- Volume :
- 59
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 38684511
- Full Text :
- https://doi.org/10.1007/s00535-024-02103-0