All ETDs from UAB

Advisory Committee Chair

Christopher A Klug

Advisory Committee Members

Donald J Buchsbaum

Janusz H Kabarowski

Richard D Lopez

Susan L Ruppert

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

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.

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