Advisor(s)
Christopher A Klug
Committee Member(s)
Donald J Buchsbaum
Janusz H Kabarowski
Richard D Lopez
Susan L Ruppert
Document Type
Dissertation
Date of Award
2013
Abstract
SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the serum proteoms of genet-ically engineered mouse models (GEM) that closely mimic the human disease state in both genetic make-up and pancreatic histopathology. In this study sought to evaluate the potential of the 2-D MALDI MS and TMT 6-plex quantitative proteomics approaches for the purposes of assaying the serum proteome of some of these GEM. The 2-D MALDI MS approach resulted in the identification of 11 proteins that were differentially abundant between control and Pdx1-Cre;LSL-KrasG12D mice which are representative of early-stage mouse PanIN (mPanIN). TheTMT 6-plex approach resulted in the identification of 50 differentially abundant proteins in similar mice. The TMT 6-plex approach was then applied to Pdx1-Cre;LSL-KrasG12D and Pdx1-Cre;LSL-KrasG12D;LSL-p53R172H (repre-sentative of later-stage mPanIN) pancreatic cancer mouse models in order to gain insight into how the serum proteome changes as early-stage pancreatic cancer progresses from mPanIN to metastatic disease, and to find novel and potentially useful biomarkers for detection of early-stage pancreatic cancer.
ProQuest Publication Number
ISBN
978-1-303-32312-6
Recommended Citation
Ludwig, Michael Robert, "Surveying the serum proteome for biomarkers of early-stage pancreatic cancer" (2013). All ETDs from UAB. 2348.
https://digitalcommons.library.uab.edu/etd-collection/2348
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