title: Expression of lysyl oxidase is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Lysyl oxidase (LOX), an extracellular matrix-remodeling enzyme, has been reported to regulate tumor metastasis. We investigated the clinical significance of LOX expression in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We examined LOX expression in ESCC cell lines by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We also examined LOX expression by real-time RT-PCR in 39 surgically resected ESCC and by immunohistochemistry in 122 surgically resected ESCC.
  
  
  RESULTS
  LOX messenger RNA (mRNA) was expressed at a high level in TTn (originating from an ESCC metastatic lesion); at a moderate level in TE-2 and TE-15; and at a low level in TE-1, TE-8, and TE-13. In Western blotting, all cell lines expressed the catalytically inactive 50-kDa LOX at approximately the same levels, but catalytically active 32-kDa LOX was overexpressed only in TTn. LOX mRNA levels in ESCC tissues were significantly higher than those observed in normal esophageal tissues (P < 0.001) and had no significant correlation with tumor-node-metastasis (TNM) factors. High LOX protein expression had a significant correlation with presence of lymph node metastasis (P = 0.009) and number of lymph node metastases (P = 0.047). Overall and cancer-specific survival rates of patients with ESCC with high LOX expression were significantly lower than those of patients with ESCC with low LOX expression (P = 0.024 and P = 0.012). Univariate and multivariate analyses revealed that high LOX protein expression was an independent prognostic factor for ESCC.
  
  
  CONCLUSIONS
  Our findings suggest that LOX can serve as a predictive marker of lymph node metastasis and prognosis in ESCC.
authors.affiliation: Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan. maksakai@med.gunma-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Sakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sano
authors.forename: Naritaka
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takanori
authors.initials: T
authors.lastname: Inose
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Sohda
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakajima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D008249:Protein-Lysine 6-Oxidase