title: Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients.
abstract: The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohistochemical staining utilizing a tissue microarray method for HLA class I APM expression showing different expression patterns among cell lines was performed for 95 surgical specimens from patients with esophageal cancer. Prognostic factors were the down-regulation of HLA-HC, and the up-regulation of β2 microglobulin and TAP-1 in the cancer tissues. Multivariate analysis using a Cox regression model indicated that the down-regulation of HLA-HC, and up-regulation of TAP-1 in cancer tissues are independent, unfavorable prognostic factors (hazard ratio, 2.361 and 2.297; P=0.0141 and 0.0145, respectively). Although there was no significant difference in survival for selected p-stage I and II patients (n=54) in all APM components, only down-regulation of HLA-HC was an unfavorable prognostic factor by a Cox regression model for selected p-stage III and IV patients (n=41). In conclusion, the current results suggest that the down-regulation of HLA-HC in tumors is especially associated with a poor prognosis among advanced esophageal cancer patients.
authors: Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648, Japan. kimitaka.t@gmail.com
authors: Kimitaka
authors: K
authors: Tanaka
authors: Takahiro
authors: T
authors: Tsuchikawa
authors: Masaki
authors: M
authors: Miyamoto
authors: Takehiro
authors: T
authors: Maki
authors: Masaomi
authors: M
authors: Ichinokawa
authors: Kanako C
authors: KC
authors: Kubota
authors: Toshiaki
authors: T
authors: Shichinohe
authors: Satoshi
authors: S
authors: Hirano
authors: Soldano
authors: S
authors: Ferrone
authors: Hirotoshi
authors: H
authors: Dosaka-Akita
authors: Yoshihiro
authors: Y
authors: Matsuno
authors: Satoshi
authors: S
authors: Kondo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D046228:Microarray Analysis; D011379:Prognosis; D015996:Survival Rate; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin