title: Association of copy number loss of CDKN2B and PTCH1 with poor overall survival in patients with pulmonary squamous cell carcinoma.
abstract: OBJECTIVE
  Although lung cancer is the leading cause of cancer deaths worldwide, reliable markers allowing prediction of patient survival at the time of initial diagnosis are still lacking. Copy number alterations (CNAs) in tumor tissue DNA have been associated with tumorigenesis and malignant progression. We aimed at identification of gene-level CNAs with prognostic value for survival in pulmonary squamous cell carcinoma (SCC).
  
  
  METHODS
  The CNA status of a panel of 44 genes was analyzed by high-resolution array comparative genomic hybridization (CGH) in 49 SCC samples. Overall survival information (median follow-up, 40 months) for the patients was collected and used to assess outcome correlations with gene CNAs.
  
  
  RESULTS
  Survival analysis showed that both CDKN2B loss and PTCH1 loss were associated with poor survival (both P < .001, log-rank test). Multivariate Cox analysis, including CDKN2B loss and PTCH1 loss as well as age, sex, cigarette smoking status, tumor size, tumor differentiation, and TNM stage showed that CDKN2B loss (hazard ratio [HR], 17.88; 95% confidence interval [CI], 4.40-72.67; P < .001) and PTCH1 loss (HR, 10.81; 95% CI, 1.92-60.98; P = .007) were independent prognostic factors for poor survival. In addition the PTCH1 loss was more frequently found in moderately or poorly differentiated tumors than in well-differentiated tumors (P = .007).
  
  
  CONCLUSIONS
  These findings suggest that 2 genes of loss, CDKN2B and PTCH1, are associated with poor overall survival in patients with SCC of the lung and may be useful as prognostic markers.
authors: Department of Cardiovascular Surgery, the Fourth Affiliated Hospital, Harbin Medical University, Heilongjiang, P.R. China.
authors: Yushi
authors: Y
authors: Zhao
authors: Ye
authors: Y
authors: Li
authors: Hongguang
authors: H
authors: Lu
authors: Jianxin
authors: J
authors: Chen
authors: Zhijie
authors: Z
authors: Zhang
authors: Zhong-Zheng
authors: ZZ
authors: Zhu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology; D055028:Comparative Genomic Hybridization / Q000379:methods; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface