title: AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients.
abstract: The growth of a tumor depends to a certain extent on an increase in mitotic events. Key steps during mitosis are the regulated assembly of the spindle apparatus and the separation of the sister chromatids. The microtubule-associated protein Aurora kinase A phosphorylates DLGAP5 in order to correctly segregate the chromatids. Its activity and recruitment to the spindle apparatus is regulated by TPX2. KIF11 and CKAP5 control the correct arrangement of the microtubules and prevent their degradation. In the present study, we investigated the role of these five molecules in non-small cell lung cancer (NSCLC). We analyzed the expression of the five genes in a large cohort of NSCLC patients (n=362) by quantitative real-time PCR. Each of the genes was highly overexpressed in the tumor tissues compared to corresponding normal lung tissue. The correlation of the expression of the individual genes depended on the histology. An increased expression of AURKA, DLGAP5, TPX2, KIF11 and CKAP5 was associated with poor overall survival (P=0.001-0.065). AURKA was a significant prognostic marker using multivariate analyses (P=0.006). Immunofluorescence studies demonstrated that the five mitosis-associated proteins co-localized with the spindle apparatus during cell division. Taken together, our data demonstrate that the expression of the mitosis-associated genes AURKA, DLGAP5, TPX2, KIF11 and CKAP5 is associated with the prognosis of NSCLC patients.
authors.affiliation: Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schneider
authors.affiliation: Department of Thoracic Oncology, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Petros
authors.initials: P
authors.lastname: Christopoulos
authors.affiliation: Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Systems Biology of Signal Transduction, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Klingmueller
authors.affiliation: Department of Thoracic Oncology, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Department of Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Felix J F
authors.initials: FJ
authors.lastname: Herth
authors.affiliation: Department of Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.affiliation: Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Nikola S
authors.initials: NS
authors.lastname: Mueller
authors.affiliation: Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Theis
authors.affiliation: Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D053208:Kaplan-Meier Estimate; D016547:Kinesins / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C454180:CKAP5 protein, human; D018797:Cell Cycle Proteins; C465041:DLGAP5 protein, human; C470243:KIF11 protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A; D016547:Kinesins