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Intraductal transplantation models of human pancreatic ductal adenocarcinoma reveal progressive transition of molecular subtypes

ABSTRACT: Intraductal transplantation models of human pancreatic ductal adenocarcinoma reveal progressive transition of molecular subtypes

PROVIDER: PRJNA637411 | ENA |

REPOSITORIES: ENA

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Intraductal transplantation models of human pancreatic ductal adenocarcinoma reveal progressive transition of molecular subtypes

Project description:Intraductal transplantation models of human pancreatic ductal adenocarcinoma reveal progressive transition of molecular subtypes

| PRJNA637412 | ENA

Intraductal Transplantation Models of Human Pancreatic Ductal Adenocarcinoma Reveal Progressive Transition of Molecular Subtypes.

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An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ.

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Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms

Project description:Circulating epithelial cells (CECs) were purified using a microfluidic device from healthy donors, patients bearing intraductal papillary mucinous neoplasms, or pancreatic ductal adenocarcinoma and their transcriptomes were sequenced.

2017-11-01 | GSE103152 | GEO

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Project description:To evaluate the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC), we performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 control samples.

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Single-cell transcriptomics of normal pancreas, intraductal papillary mucinous neoplasm, and pancreatic adenosquamous carcinoma reveals the heterogeneous progression of pancreatic ductal and stromal cells

Project description:Background: Single-cell RNA sequencing (scRNA-seq) contributes to discovering intrinsic heterogeneity of pancreatic adenosquamous carcinoma (PASC), a lethal human malignancy. However, the gene-pattern variations within ductal and stromal cells remain unclear. Methods: We fulfilled scRNA-seq profiling with one healthy donor pancreas, one intraductal papillary mucinous neoplasm (IPMN), and one PASC sample tissue. Multiple bioinformatics analyses were used to investigate the transcriptomics abnormalities from normal stage to tumor formation. Results: We identified ten subpopulations from 10,346 single cells, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and malignant cells. Within our analysis, pancreatic cancer cells were further divided into five clusters; notably, cluster 1 exhibited stem-like phenotypes, such as UBE2C, ASPM, and TOP2A. We also found that S100A2 could be a specific biomarker for tumor cells, relating to PASC progression. LGALS1, NPM1, RACK1, and PERP were upregulated gradually from ductal to malignant cells. Furthermore, the level of copy number variation in ductal and cancer cells was significantly greater than reference cells. The expression of EREG, FCGR2A, FCGR2A, and CCL4L2 increased in myeloid cells along with tumor development, while cancer-associated fibroblast could induce the immunosuppressive tumor microenvironment, promoting pancreatic cancerogenesis. Finally, we demonstrated that EGFR-associated ligand-receptor pairs were activated in stromal to malignant cell communication. Conclusion: This study revealed the variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered cellular interactions following PASC progression. Thus, we provided valuable information to further understand the crucial regulatory mechanisms that embrace the potential therapeutic targets for PASC.

2021-08-03 | GSE165399 | GEO

Pervasive subtypes of pancreatic ductal adenocarcinoma (PDA) and their differing response to therapy.

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Virtual Microdissection of Pancreatic Ductal Adenocarcinoma Reveals Tumor and Stroma Subtypes.

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here, we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, which includes primary, metastatic, and normal samples. By digitally separating tumor, stroma, and normal gene expression, we have identified and validated two tumor-specific subtypes including a â€œbasal-likeâ€ subtype which has worse outcome, and is molecularly similar to basal tumors in bladder and breast cancer. Furthermore, we define 'normal' and 'activated' stromal subtypes which are independently prognostic. Our results provide new insight into the molecular composition of PDAC which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies is critical. Analysis of the landscape of gene expression in pancreatic adenocarcinoma. Data include 145 primary and 61 metastatic PDAC tumors, 17 cell lines, 46 pancreas and 88 distant site adjacent normal samples. Arrays represent distinct samples. The SPOT column in the raw data file (linked to each sample record) contains Agilent feature extraction numbers (included in the 'GPL4133-20424.txt' linked to the platform records).

2015-09-07 | E-GEOD-71729 | biostudies-arrayexpress

Pervasive subtypes of pancreatic ductal adenocarcinoma (PDA) and their differing response to therapy.

Project description:Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA. RNA was extracted from archival patient FFPE PDA samples and hybridized on Affymetrix U133 plus 2.0 microarrays. The CEL files were processed using R based Bioconductor and normalized values were obtained using RMA. RNA was extracted from human PDA cell line samples and hybridized on Affymetrix U133 plus 2.0 microarrays. The CEL files were processed using R based Bioconductor and normalized values were obtained using RMA. RNA was extracted from mouse PDA cell lines and hybridized on Affymetrix Mouse 430a 2.0 microarrays. The CEL files were processed using R based Bioconductor and normalized values were obtained using RMA.

2011-04-01 | E-GEOD-17891 | biostudies-arrayexpress

Virtual Microdissection of Pancreatic Ductal Adenocarcinoma Reveals Tumor and Stroma Subtypes.

2015-09-07 | GSE71729 | GEO

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