In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14689-e14689
Abstract:
e14689 Background: EAC from BE is increasing, and prognosis is poor. Representative models are critical to understanding BE/EAC and developing therapies. We refined the Levrat’s model of BE/EAC and showed that a SMO inhibitor prevented BE/EAC (Proc ASCO 2012). To validate the rat model as representative of human and explore differentially expressed proteins/pathways, we evaluated the proteomic profiles of nl/BE/EAC from humans and rats. Methods: GE reflux was induced in 6-8 wk old male Sprague–Dawley rats by the Levrat’s procedure--approved by the IACUC. Incidence of BE/EAC at 28 wks was 90%/70%. Human nl/BE/EAC samples were obtained from the PENG database--IRB approved. Histology confirmed by a single pathologist (JD). Following LCM from paraffin, digests were analyzed in triplicate by nanoflow LC-MS/MS with a hybrid linear ion trap-Orbitrap Velos mass spectrometer followed by online nanoflow LC. Mass spectral data representing ~ 20-30,000 CID spectra were searched, and a quantitative estimate of relative abundance was obtained. Kruskal-Wallis non-parametric ANOVA was employed, and clusters were compared within and between humans and rats. Results: Data is available for rat tissues, 10 samples each for nl/BE/EAC. Heirarchical clustering of 410 features yielded 3 statistically significantly distinct groups corresponding to normal, BE and EAC (ANOVA p 〈 0.001). Pair-wise comparison between groups yielded statistically significant (p 〈 0.05) differential protein expression as follows: nl vs BE~550; nl vs EAC~450; BE vs EAC~150. For EAC, proteins were differentially expressed in pathways including: protein degradation/synthesis, cell death, growth and proliferation (NF-kB, EIF4A, Akt, b-tubulin). Analysis of human tissues and comparison to rat will be presented at the meeting. Conclusions: Proteomic evaluation of normal/BE/EAC tissues from the Levrat’s model of BE/EAC yielded distinct protein patterns for nl/BE/EAC. Proteins differentially expressed in EAC vs normal/EAC are involved in cancer related pathways. Differentially expressed proteins may provide targets for therapy, which could be tested in the Levrat’s model.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e14689
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
