title: Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients.
abstract: BACKGROUND
  Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases.
  
  
  METHODS
  Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival.
  
  
  RESULTS
  PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ(2)=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ(2)=20.486, P<0.001).
  
  
  CONCLUSIONS
  Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC.
authors.affiliation: 1 Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China ; 2 Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Yun-En
authors.initials: YE
authors.lastname: Lin
authors.affiliation: 1 Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China ; 2 Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Qi-Nian
authors.initials: QN
authors.lastname: Wu
authors.affiliation: 1 Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China ; 2 Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Lin
authors.affiliation: 1 Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China ; 2 Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Guang-Qiu
authors.initials: GQ
authors.lastname: Li
authors.affiliation: 1 Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China ; 2 Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Zhang
keywords: Non-small-cell lung cancer (NSCLC); immunohistochemistry (IHC); paired basic amino acid-cleaving enzyme 4 (PACE4); prognosis