title: Membranous expression of activated leukocyte cell adhesion molecule contributes to poor prognosis and malignant phenotypes of non-small-cell lung cancer.
abstract: BACKGROUND
  Activated leukocyte cell adhesion molecule (ALCAM) has been shown to correlate with the prognosis of patients with various types of human malignancies. However, the relationship between ALCAM expression and progression of non-small-cell lung cancer (NSCLC) has not been investigated. This study was designed to clarify the prognostic impact of ALCAM expression of NSCLC cells.
  
  
  METHODS
  The study population consisted of 147 NSCLC patients who underwent complete resection. We performed immunohistochemical staining for ALCAM expression and correlated this to the clinicopathologic parameters and patient survival. The ALCAM expression in NSCLC cell lines was analyzed using quantitative reverse transcription-polymerase chain reaction and Western blot analyses. ALCAM knockdown in NSCLC cell lines was performed with lentivirus-mediated short hairpin RNA transduction.
  
  
  RESULTS
  Positive membranous and cytoplasmic ALCAM expressions were detected in 66 (44.9%) and 57 (38.8%) patients, respectively. A significant association of high membranous ALCAM expression with shortened overall survival (OS) was found (P = 0.009). However, patients with cytoplasmic staining of ALCAM showed no significantly shortened OS (P = 0.723). Multivariate analyses showed that membranous expression was adverse prognostic factors for OS (hazard ratio, 2.11; P = 0.046). ALCAM knockdown with short hairpin RNA suppressed cell migration and invasion of NSCLC cell lines in vitro.
  
  
  CONCLUSIONS
  Strong membranous ALCAM expression is associated with a poor prognosis in patients with resected NSCLC, and overexpression of ALCAM causes malignant phenotypes of NSCLC.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Ishiguro
authors.forename: Hideki
authors.initials: H
authors.lastname: Murakami
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Makiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Usami
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Osada
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D012189:Retrospective Studies
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D034741:RNA, Small Interfering