title: Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin.
abstract: Recent advances in two-dimensional electrophoresis (2-DE) such as fluorescent 2-D differential gel electrophoresis (2-D DIGE) has made it possible to detect and quantitate the critical changes involved in disease pathogenesis. We have previously identified novel proteins with altered expression in primary colorectal cancer using agarose 2-DE that has a higher loading capacity than immobilized pH gradient gel. The aim of this study is to identify novel proteins with altered expression in primary esophageal cancer using the powerful method of agarose 2-DE and agarose 2-D DIGE. Excised tissues from 12 patients of primary esophageal cancer were obtained. Proteins with altered expression between cancer and adjacent non-cancer tissues were analyzed by agarose 2-D DIGE and identified by mass spectrometry. Thirty-three proteins out of 74 spots with altered expression in tumors were identified. Among them, a 195-kDa protein, periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and scarcely expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression.
authors.affiliation: Department of Academic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Nishimori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsushita
authors.forename: Masamichi
authors.initials: M
authors.lastname: Oh-Ishi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Maeda
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Takenori
authors.initials: T
authors.lastname: Ochiai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary; D002448:Cell Adhesion; D018450:Disease Progression; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004848:Epithelium / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010449:Peptide Mapping; D051179:Plakins / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D051179:Plakins; C110037:Ppl protein, mouse; D020543:Proteome