title: Aberrant expression of proteins involved in signal transduction and DNA repair pathways in lung cancer and their association with clinical parameters.
abstract: BACKGROUND
  Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues.
  
  
  RESULTS
  We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA) assay. The results showed that 18 molecules were significantly different (p<0.05) by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction and lipid metabolism, or function as cell surface/matrix proteins. We also validated RPPA results by Western blot and/or immunohistochemical analyses for some of those molecules. Statistical analyses showed that Ku80 levels were significantly higher in tumors of nonsmokers than in those of smokers. Cyclin B1 levels were significantly overexpressed in poorly differentiated tumors while Cox2 levels were significantly overexpressed in neuroendocrinal tumors. A high level of Stat5 is associated with favorable survival outcome for patients treated with surgery.
  
  
  CONCLUSIONS
  Our results revealed that some molecules involved in DNA damage/repair, signal transductions, lipid metabolism, and cell proliferation were drastically aberrant in lung cancer tissues, and Stat5 may serve a molecular marker for prognosis of lung cancers.
authors.affiliation: Department of Thoracic Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hofstetter
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wenxian
authors.initials: W
authors.lastname: Hu
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Apar
authors.initials: A
authors.lastname: Pataer
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Yiling
authors.initials: Y
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.forename: Lauren Averett
authors.initials: LA
authors.lastname: Byers
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
mesh_terms: D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D049109:Cell Proliferation; D004260:DNA Repair / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis; D010766:Phosphorylation; D011379:Prognosis; D040901:Proteomics; D050799:STAT5 Transcription Factor / Q000032:analysis; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D050799:STAT5 Transcription Factor