title: Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers.
abstract: 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.
authors.affiliation: Nashville Veterans Affairs Medical Center, Vanderbilt University School of Medicine, Tennessee, USA.
authors.forename: Josane F
authors.initials: JF
authors.lastname: Sousa
authors.forename: Amy-Joan L
authors.initials: AJ
authors.lastname: Ham
authors.forename: Corbin
authors.initials: C
authors.lastname: Whitwell
authors.forename: Ki Taek
authors.initials: KT
authors.lastname: Nam
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Bonnie
authors.initials: B
authors.lastname: LaFleur
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Liebler
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D019070:Cell Lineage; D051152:Clusterin / Q000378:metabolism; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007781:Lactoferrin / Q000378:metabolism; D008679:Metaplasia; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D010455:Peptides / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D051152:Clusterin; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C490098:LTF protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins; C451060:spasmolytic polypeptide; D007781:Lactoferrin