title: Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  CRNN gene expression is downregulated in esophageal squamous cell carcinoma (ESCC), although its clinical implications in esophageal cancer remain unclear.
  
  
  METHODS
  We performed integrated microarray analysis and identified the CRNN gene as 1 of the major downregulated genes in ESCC. CRNN downregulation was validated at the nucleic acid level in 16 ESCC cases using complementary DNA microarray and at the protein level by immunohistochemical stains in an additional 220 ESCC cases. The clinicopathologic relevance and prognostic significance of CRNN expression in ESCC were explored.
  
  
  RESULTS
  Downregulated CRNN expression was noted at the messenger RNA and protein levels. Immunohistochemical staining revealed negative and positive CRNN expression in 171 (77.7%) and 49 (22.3%) patients with ESCC, respectively. Patients with negative CRNN protein expression had an advanced tumor invasion depth (P = .002), advanced nodal involvement (P = .014), and longer tumor length (P = .037). Patients with negative CRNN expression (median survival, 14.0 months; 5-year survival rate, 20.5%) had poorer overall survival than those with positive expression (30.0 months and 40.3%, respectively; P = .006). On multivariate analysis, negative CRNN expression, nodal involvement, and distant metastasis remained significant prognostic factors for poor overall survival (negative vs positive CRNN, hazard ratio, 1.464; P = .047).
  
  
  CONCLUSIONS
  Our analysis has highlighted the clinical implications of CRNN expression in ESCC. Loss of CRNN expression correlated with advanced tumor length, greater tumor invasion depth, lymph node metastasis, and poor survival in patients with ESCC.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan; National Yang-Ming University School of Medicine, Taipei City, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Po-Kuei
authors.initials: PK
authors.lastname: Hsu
authors.affiliation: National Yang-Ming University School of Medicine, Taipei City, Taiwan; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Kao
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei City, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Chueh-Chuan
authors.initials: CC
authors.lastname: Yen
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan; National Yang-Ming University School of Medicine, Taipei City, Taiwan.
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: National Yang-Ming University School of Medicine, Taipei City, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei City, Taiwan; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan. Electronic address: tychou@vghtpe.gov.tw.
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C418764:CRNN protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger