title: USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis.
  
  
  METHODS
  In this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software.
  
  
  RESULTS
  We observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.
  
  
  CONCLUSIONS
  Up-regulation of USP9X plays an important role in formation and progression of precancerous lesions in ESCC and USP9X expression levels were significantly correlated with the survival of ESCC patients. Thus, USP9X could be considered as a potential biomarker and prognostic predictor for ESCC.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1945302932102737.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.forename: Qian
authors.initials: Q
authors.lastname: Hu
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: He
authors.forename: Ling
authors.initials: L
authors.lastname: Cui
authors.forename: Xinlian
authors.initials: X
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Hongqian
authors.initials: H
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu 610041, China. sunny630@126.com.
authors.forename: Shanling
authors.initials: S
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C506234:USP9X protein, human; D043222:Ubiquitin Thiolesterase