title: Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma.
abstract: BACKGROUND
  The correlation of S-phase kinase-associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp2 evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp2 on survival.
  
  
  METHODS
  Tissue microarrays that included 157 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of Skp2 expression was analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. The prognostic impact of clinicopathologic variables and Skp2 expression was evaluated using a Cox proportional hazards model. A cell proliferation assay and a colony formation assay were performed in ESCC cell lines to determine the function of Skp2 on the progression of ESCC in vitro.
  
  
  RESULTS
  Skp2 expression correlated closely with the T category (p = 0.035) and the pathological tumor-node-metastasis (TNM) stage (p = 0.027). High expression of Skp2 was associated with poor overall survival in resectable ESCC (p = 0.01). The multivariate Cox regression analysis demonstrated that pathological T category, pathological N category, cell differentiation, and negative Skp2 expression were independent factors for better overall survival. In vitro assays of ESCC cell lines demonstrated that Skp2 promoted the proliferative and colony-forming capacity of ESCCs.
  
  
  CONCLUSIONS
  Negative Skp2 expression in primary resected ESCC is an independent factor for better survival. Skp2 may play a pro-proliferative role in ESCC cells.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.forename: Xue
authors.initials: X
authors.lastname: Hou
authors.forename: Qian
authors.initials: Q
authors.lastname: Cui
authors.forename: Tie-Bang
authors.initials: TB
authors.lastname: Kang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Fu
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.forename: Jie-Hua
authors.initials: JH
authors.lastname: He
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Hao-Xian
authors.initials: HX
authors.lastname: Yang
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D016019:Survival Analysis; D014410:Tumor Stem Cell Assay
chemical_list: D007976:Leupeptins; D061988:Proteasome Inhibitors; D044786:S-Phase Kinase-Associated Proteins; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde