Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers.

Sousa JF, Ham AJ, Whitwell C, Nam KT, Lee HJ, Yang HK, Kim WH, Zhang B, Li M, LaFleur B, Liebler DC, Goldenring JR
Am J Pathol. 2012 181 (5): 1560-72

PMID: 22944598 · PMCID: PMC3483808 · DOI:10.1016/j.ajpath.2012.07.027

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.

Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

MeSH Terms (23)

Biomarkers, Tumor Calcium-Binding Proteins Cell Lineage Clusterin Disease Progression DNA-Binding Proteins Gastric Mucosa Humans Intercellular Signaling Peptides and Proteins Lactoferrin Metaplasia Models, Biological Neoplasm Proteins Neoplasm Staging Paraffin Embedding Peptides Proteomics Receptors, Cell Surface Stomach Stomach Neoplasms Trefoil Factor-2 Tumor Suppressor Proteins Up-Regulation

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