Abstract/Details

Liquid chromatography – mass spectrometry for protein biomarker discovery in pancreatic adenocarcinoma


2011 2011

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Abstract (summary)

Pancreatic cancer is a devastating disease with one of the lowest survival rates of all cancers, partly due to the difficulty of detection in its early stages. Recent developments in liquid chromatography – mass spectrometry (LC-MS) technology have made it possible to profile proteins associated with disease in a comprehensive manner. This work sought to apply current LC-MS methodology to the problem of pancreatic cancer.

A comprehensive list of proteins secreted by the tumor microenvironment was compiled in the first aim. Culture of human pancreatic cell lines, both cancerous and stromal, was used to simulate the tumor microenvironment in vitro and produce a proteome rich in potential biomarkers. The proteins identified in this analysis demonstrated the complex signals pancreatic tumor cells use to communicate with their environment and might encompass therapeutic targets and biomarkers.

To measure the levels of these proteins in human serum, a relative quantitative LC-MS method was developed in the second aim. Traditional bioanalytical techniques were incorporated to enhance the utility of the method. Multiple reaction monitoring (MRM)/MS provided sensitivity and specificity to the method and stable isotope dilution (SID) provided correction for losses during sample preparation and analysis that enabled precise quantitation. The multiplexed method efficiently determined the concentration of over 70 proteins in a single analysis.

In the third aim, the relative quantitative method was used to compare a panel of putative protein biomarkers in human pancreatic cancer and control serum. This analysis identified 15 differential proteins with the ability to discriminate pancreatic cancer subjects from their age-matched controls with sensitivity and specificity superior to any other reported pancreatic cancer biomarkers. Future validation of this panel could change the way we diagnose pancreatic cancer.

Indexing (details)


Subject
Pharmacology;
Analytical chemistry
Classification
0419: Pharmacology
0486: Analytical chemistry
Identifier / keyword
Health and environmental sciences; Pure sciences; Biomarker discovery; Pancreatic cancer; Proteomics
Title
Liquid chromatography – mass spectrometry for protein biomarker discovery in pancreatic adenocarcinoma
Author
Wehr, Angela Y.
Number of pages
199
Publication year
2011
Degree date
2011
School code
0175
Source
DAI-B 73/03, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781267026750
Advisor
Blair, Ian A.
University/institution
University of Pennsylvania
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3485742
ProQuest document ID
908421455
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/908421455
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