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Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma

Overview of attention for article published in BMC Cancer, August 2016
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Title
Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma
Published in
BMC Cancer, August 2016
DOI 10.1186/s12885-016-2540-6
Pubmed ID
Authors

Rekin’s Janky, Maria Mercedes Binda, Joke Allemeersch, Anke Van den broeck, Olivier Govaere, Johannes V. Swinnen, Tania Roskams, Stein Aerts, Baki Topal

Abstract

Pancreatic cancer is poorly characterized at genetic and non-genetic levels. The current study evaluates in a large cohort of patients 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 histologically normal pancreatic tissue samples. Cox regression models were used to study the effect on survival of molecular subtypes and 16 clinicopathological prognostic factors. In order to better understand the biology of PDAC we used iRegulon to identify transcription factors (TFs) as master regulators of PDAC and its subtypes. We confirmed the PDAssign gene signature as classifier of PDAC in molecular subtypes with prognostic relevance. We found molecular subtypes, but not clinicopathological factors, as independent predictors of survival. Regulatory network analysis predicted that HNF1A/B are among thousand TFs the top enriched master regulators of the genes expressed in the normal pancreatic tissue compared to the PDAC regulatory network. On immunohistochemistry staining of PDAC samples, we observed low expression of HNF1B in well differentiated towards no expression in poorly differentiated PDAC samples. We predicted IRF/STAT, AP-1, and ETS-family members as key transcription factors in gene signatures downstream of mutated KRAS. PDAC can be classified in molecular subtypes that independently predict survival. HNF1A/B seem to be good candidates as master regulators of pancreatic differentiation, which at the protein level loses its expression in malignant ductal cells of the pancreas, suggesting its putative role as tumor suppressor in pancreatic cancer. The study was registered at ClinicalTrials.gov under the number NCT01116791 (May 3, 2010).

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 90 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 2%
France 1 1%
Unknown 87 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 22%
Researcher 16 18%
Student > Master 11 12%
Student > Bachelor 10 11%
Student > Doctoral Student 4 4%
Other 12 13%
Unknown 17 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 28 31%
Medicine and Dentistry 21 23%
Agricultural and Biological Sciences 11 12%
Chemistry 2 2%
Nursing and Health Professions 1 1%
Other 5 6%
Unknown 22 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 August 2016.
All research outputs
#7,117,158
of 8,223,523 outputs
Outputs from BMC Cancer
#2,807
of 3,468 outputs
Outputs of similar age
#198,120
of 233,174 outputs
Outputs of similar age from BMC Cancer
#186
of 264 outputs
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