Early diagnosis and curative resection are the predominant factors associated with increased survival in patients with gastric cancer. However, most gastric cancer cases are still diagnosed at later stages. Since most pathologic specimens are archived as FFPE samples, the ability to use them to generate expression profiles can greatly improve cancer biomarker discovery. We sought to uncover new biomarkers for stomach preneoplastic metaplasias and neoplastic lesions by generating proteome profiles using FFPE samples. We combined peptide isoelectric focusing and liquid chromatography-tandem mass spectrometry analysis to generate proteomic profiles from FFPE samples of intestinal-type gastric cancer, metaplasia, and normal mucosa. The expression patterns of selected proteins were analyzed by immunostaining first in single tissue sections from normal stomach, metaplasia, and gastric cancer and later in larger tissue array cohorts. We detected 60 proteins up-regulated and 87 proteins down-regulated during the progression from normal mucosa to metaplasia to gastric cancer. Two of the up-regulated proteins, LTF and DMBT1, were validated as specific markers for spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia, respectively. In cancers, significantly lower levels of DMBT1 or LTF correlated with more advanced disease and worse prognosis. Thus, proteomic profiling using FFPE samples has led to the identification of two novel markers for stomach metaplasias and gastric cancer prognosis.
Bibliographical noteFunding Information:
These studies were supported by NIH grant RO1 DK071590 (J.R.G.), American Recovery & Reinvestment Act of 2009 Supplemental Funding grant RO1 DK071590-S1 (J.R.G.), and Core Resources supported by the Vanderbilt Digestive Disease Center grant P30 DK058404 , and the Vanderbilt-Ingram Cancer Center through NCI Cancer Center support grant P30 CA068485 using the Pathology Shared Resource. These studies also used Ariol SL-50 imaging in the Epithelial Biology Center Shared Imaging Resource.
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine