Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA125999 | ENA |
REPOSITORIES: ENA
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Project description:A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma Pancreatic ductal adenocarcinoma (PDAC), comprising over 90% of all pancreatic cancers, remains a lethal disease with an estimated 232,000 new cases, 227,000 deaths per year worldwide, and a less than 5% five-year survival rate. Currently the standard of care for the 20% of patients with localized disease is surgery followed by chemotherapy, and in some cases radiation. Unfortunately despite the use of adjuvant therapy, median survival remains at best 23 months. It is important to note however, that up to 27% of patients with resected PDAC can survive for five years. However, in these studies examining actual long-term survivors, only two have found that adjuvant therapy was associated with improved survival. In addition, randomized controlled trials of gemcitabine-based chemotherapy demonstrate an improvement in median survival of at best 3 months. One possible conclusion from these studies is that tumor biology dictates outcome and that our current adjuvant therapy has only a modest impact on altering a patient's course.Hypothesizing that the dismal outcome of patients with localized disease is due to the presence of micrometastasic disease, current clinical investigation has focused on preoperative or neoadjuvant therapy. This approach, where patients who cannot tolerate the stress of therapy or develop metastatic disease during treatment are spared surgery, has demonstrated an overall survival of 34 months in this highly selected patient population. Therefore the ability to select patients who would most benefit from a neoadjuvant approach may be important. One way to do this is to define a prognostic gene signature that can identify patients with more aggressive tumor biology upfront. reference x sample The 30 Nebraska and UNC samples were not analyzed with clinical data so it is not provided. One of the PE samples is missing some clinical data.
2010-07-18 | E-GEOD-21501 | biostudies-arrayexpress
Project description:A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma Pancreatic ductal adenocarcinoma (PDAC), comprising over 90% of all pancreatic cancers, remains a lethal disease with an estimated 232,000 new cases, 227,000 deaths per year worldwide, and a less than 5% five-year survival rate. Currently the standard of care for the 20% of patients with localized disease is surgery followed by chemotherapy, and in some cases radiation. Unfortunately despite the use of adjuvant therapy, median survival remains at best 23 months. It is important to note however, that up to 27% of patients with resected PDAC can survive for five years. However, in these studies examining actual long-term survivors, only two have found that adjuvant therapy was associated with improved survival. In addition, randomized controlled trials of gemcitabine-based chemotherapy demonstrate an improvement in median survival of at best 3 months. One possible conclusion from these studies is that tumor biology dictates outcome and that our current adjuvant therapy has only a modest impact on altering a patient's course.Hypothesizing that the dismal outcome of patients with localized disease is due to the presence of micrometastasic disease, current clinical investigation has focused on preoperative or neoadjuvant therapy. This approach, where patients who cannot tolerate the stress of therapy or develop metastatic disease during treatment are spared surgery, has demonstrated an overall survival of 34 months in this highly selected patient population. Therefore the ability to select patients who would most benefit from a neoadjuvant approach may be important. One way to do this is to define a prognostic gene signature that can identify patients with more aggressive tumor biology upfront.
2010-07-19 | GSE21501 | GEO
Project description:Whole-Tissue Gene Expression Study of Pancreatic Ductal Adenocarcinoma
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Project description:Transcription profiling by 3'-end sequencing of whole blood from pancreatic ductal adenocarcinoma (PDAC) patients and healthy controls for PDAC diagnosis
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Project description:Oncogenic KRAS rewires pancreatic ductal adenocarcinoma (PDAC) metabolism to promote dependence on autophagy and iron metabolism. NCOA4-mediated ferritinophagy links autophagy and iron metabolism as NCOA4 selectively targets ferritin, the cellular iron storage complex, via autophagy to the lysosome for ferritin degradation and release of iron for utilization. Using patient-derived and genetically engineered murine models of PDAC we now demonstrate that ferritinophagy is upregulated in PDAC to sustain iron availability thereby promoting PDAC progression. PDAC global quantitative proteomics reveals that ferritinophagy fuels iron-sulfur cluster synthesis to support mitochondrial homeostasis. Targeting NCOA4 leads to tumor growth delay and prolonged survival but with development of compensatory iron acquisition pathways. Finally, a ferritinophagy gain-of-function PDAC murine model demonstrates worse survival, and an elevated ferritinophagy expression signature predicts for worse overall survival in human PDAC patients. Together, our data define NCOA4-mediated ferritinophagy as a therapeutic target in PDAC and reveal that maintenance of cellular iron homeostasis is a critical cell autonomous function of PDAC autophagy.
2022-08-17 | PXD033356 | Pride
Project description:To further develop our understanding of the gene expression signature of pancreatic ductal adenocarcinoma Gene expression signatures in macrodissected resected pancreatic ductal adenocarcinoma specimens
2014-03-14 | E-GEOD-55643 | biostudies-arrayexpress
Project description:Identification of carcinogenesis and tumor progression processes in pancreatic ductal adenocarcinoma using high-throughput proteomics
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Project description:Analysis of expression profile of peripheral blood from pancreatic ductal adenocarcinoma patients RNA expression profile of peripheral blood from pancreatic ductal adenocarcinoma patients
2015-11-04 | GSE74629 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGFβ-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men. KC (Atm+/+) and AKC (Atm-/-) mouse pancreata at 5 weeks old (n= 3 KC; n= 3 AKC) or 10 weeks old (n=3 KC; n=4 AKC) were subjected to microarray analysis.
2015-08-07 | E-GEOD-68808 | biostudies-arrayexpress
Project description:Transcription profiling by array of normal pancreas, primary pancreatic ductal adenocarcinoma (PDAC), normal liver, and pancreatic liver metastases using the Affymetrix HG-U133B array
2025-01-24 | E-GEOD-19280 | ExpressionAtlas