title: Elevated expression of CDK4 in lung cancer.
abstract: BACKGROUND
  The aim of the present study was to analyze the expression of Cyclin-dependent kinase 4 (CDK4) in lung cancer and its correlation with clinicopathologic features. Furthermore, the involvement of CDK4-mediated cell cycle progression and its molecular basis were investigated in the pathogenesis of lung cancer.
  
  
  METHODS
  Using immunohistochemistry analysis, we analyzed CDK4 protein expression in 89 clinicopathologically characterized lung cancer patients (59 males and 30 females) with ages ranging from 36 to 78 years and compared them to 23 normal lung tissues. Cases with cytoplasmic and nuclear CDK4 immunostaining score values greater than or equal to 7 were regarded as high expression while scores less than 7 were considered low expression. The correlation between the expression level of CDK4 and clinical features was analyzed. Furthermore, we used lentiviral-mediated shRNA to suppress the expression of CDK4 and investigate its function and molecular mechanism for mediating cell cycle progression.
  
  
  RESULTS
  The expression level of CDK4 protein was significantly increased in lung cancer tissues compared to normal tissues (P < 0.001). In addition, high levels of CDK4 protein were positively correlated with the status of pathology classification (P = 0.047), lymph node metastasis (P = 0.007), and clinical stage (P = 0.004) of lung cancer patients. Patients with higher CDK4 expression had a markedly shorter overall survival time than patients with low CDK4 expression. Multivariate analysis suggested the level of CDK4 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with lung cancer. Use of lentiviral-mediated shRNA to inhibit the expression of CDK4 in lung cancer cell line A549 not only inhibited cell cycle progression, but also dramatically suppressed cell proliferation, colony formation, and migration. Furthermore, suppressing CDK4 expression also significantly elevated the expression of cell cycle regulator p21
  
  
  CONCLUSIONS
  Overexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer.
authors.affiliation: Cancer Research Institute of Southern Medical University, 510515 Guangzhou, PR China.
authors.forename: Aibing
authors.initials: A
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Guo
authors.forename: Weiren
authors.initials: W
authors.lastname: Luo
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhen
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Yang
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4