title: Elevated nuclear CCND1 expression confers an unfavorable prognosis for early stage lung adenocarcinoma patients.
abstract: OBJECTIVE
  To examine the expression pattern of CCND1 and analyze the correlation of its nuclear expression with clinicopathologic features and prognosis in lung adenocarcinoma.
  
  
  METHODS
  CCND1 mRNA and protein levels in lung adenocarcinoma tissues were examined. The relationship between nuclear CCND1 protein expression and clinical features including survival prognosis was analyzed.
  
  
  RESULTS
  CCND1 mRNA levels were markedly increased in lung adenocarcinoma (P=0.0019). Western blot analysis confirmed increased nuclear CCND1 protein expression in lung adenocarcinoma specimens. Immunohistochemistry analysis confirmed that CCND1 protein was predominantly nuclear localized in lung adenocarcinoma cells and significantly elevated relative to normal lung tissues (P<0.001). Furthermore, high levels of nuclear CCND1 were positively correlated with clinical stage (P=0.026). Patients with nuclear CCND1 expression had a significantly shorter overall survival time than did patients with low expression. Interestingly, nuclear CCND1 expression in clinical stage I+II, but not clinical stage III, was shown associated with poor prognosis and shorter overall survival time for lung adenocarcinoma patients by strata analysis. Finally, nuclear CCND1 expression tended to be an independent prognostic indicator (P=0.087) for lung adenocarcinoma patient survival.
  
  
  CONCLUSIONS
  Increased nuclear CCND1 is a potential unfavorable prognostic factor for lung adenocarcinoma patients, especially those with clinical early stage (stage I+II).
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical UniversityGuangzhou, Guangdong, PR China; Peking University Shenzhen HospitalShenzhen, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical University Guangzhou, Guangdong, PR China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical UniversityGuangzhou, Guangdong, PR China; Dpartment of Pathology, School of Basic Medicine, Guangzhou Medical CollegeGuangzhou, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical University Guangzhou, Guangdong, PR China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical University Guangzhou, Guangdong, PR China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical University Guangzhou, Guangdong, PR China.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Cancer Center, TCM-Integrated Hospital, Southern Medical UniversityGuangzhou, Guangdong, PR China; Cancer Research Institute, Southern Medical UniversityGuangzhou, PR China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry* / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1
keywords: CCND1; lung adenocarcinoma; nuclear expression