Type

Journal Article

Authors

Martin Clynes
Paula Meleady
Michael Moriarty
Gerard McVey
Robert M Straubinger
Ninfa L Straubinger
Vincent Lynch
Kevin C Conlon
Justin Geoghegan
Neil T. Conlon
and 8 others

Subjects

Biochemistry

Topics
stromal cells pancreatic cancer membrane enriched data analysis therapeutic targets adc therapy quantitative analysis survival rate pdx pancreatic ductal adenocarcinoma pdac human cells proteomics disease progression human tissue analysis

A Comparative Quantitative LC-MS/MS Profiling Analysis of Human Pancreatic Adenocarcinoma, Adjacent-Normal Tissue, and Patient-Derived Tumour Xenografts. (2018)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide; it develops in a relatively symptom-free manner, leading to rapid disease progression and metastasis, leading to a 5-year survival rate of less than 5%. A lack of dependable diagnostic markers and rapid development of resistance to conventional therapies are among the problems associated with management of the disease. A better understanding of pancreatic tumour biology and discovery of new potential therapeutic targets are important goals in pancreatic cancer research. This study describes the comparative quantitative LC-MS/MS proteomic analysis of the membrane-enriched proteome of 10 human pancreatic ductal adenocarcinomas, 9 matched adjacent-normal pancreas and patient-derived xenografts (PDXs) in mice (10 at F1 generation and 10 F2). Quantitative label-free LC-MS/MS data analysis identified 129 proteins upregulated, and 109 downregulated, in PDAC, compared to adjacent-normal tissue. In this study, analysing peptide MS/MS data from the xenografts, great care was taken to distinguish species-specific peptides definitively derived from human sequences, or from mice, which could not be distinguished. The human-only peptides from the PDXs are of particular value, since only human tumour cells survive, and stromal cells are replaced during engraftment in the mouse; this list is, therefore, enriched in tumour-associated proteins, some of which might be potential therapeutic or diagnostic targets. Using human-specific sequences, 32 proteins were found to be upregulated, and 113 downregulated in PDX F1 tumours, compared to primary PDAC. Differential expression of CD55 between PDAC and normal pancreas, and expression across PDX generations, was confirmed by Western blotting. These data indicate the value of using PDX models in PDAC research. This study is the first comparative proteomic analysis of PDAC which employs PDX models to identify patient tumour cell-associated proteins, in an effort to find robust targets for therapeutic treatment of PDAC.
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Full list of authors on original publication

Martin Clynes, Paula Meleady, Michael Moriarty, Gerard McVey, Robert M Straubinger, Ninfa L Straubinger, Vincent Lynch, Kevin C Conlon, Justin Geoghegan, Neil T. Conlon and 8 others

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 232
 
2
Paula Meleady
Dublin City University
Total Publications: 115
 
3
Michael Moriarty
Dublin City University
 
4
Vincent Lynch
Dublin City University
Total Publications: 12
 
5
K C Conlon
TU Dublin (Tallaght Campus)
Total Publications: 59
 
6
Justin Geoghegan
Trinity College Dublin
Total Publications: 14
 
7
Neil T. Conlon
Dublin City University
Total Publications: 10