AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients

被引:121
作者
Schneider, Marc A. [1 ,8 ]
Christopoulos, Petros [2 ,8 ]
Muley, Thomas [1 ,8 ]
Warth, Arne [5 ,8 ]
Klingmueller, Ursula [6 ,8 ,9 ]
Thomas, Michael [2 ,8 ]
Herth, Felix J. F. [3 ,8 ]
Dienemann, Hendrik [4 ,8 ]
Mueller, Nikola S. [7 ,9 ]
Theis, Fabian [7 ,9 ]
Meister, Michael [1 ,8 ,9 ]
机构
[1] Univ Heidelberg Hosp, Thoraxklin, Translat Res Unit, Roentgenstr 1, D-69126 Heidelberg, Germany
[2] Univ Heidelberg Hosp, Thoraxklin, Dept Thorac Oncol, Heidelberg, Germany
[3] Univ Heidelberg Hosp, Thoraxklin, Dept Pneumol & Crit Care Med, Heidelberg, Germany
[4] Univ Heidelberg Hosp, Thoraxklin, Dept Surg, Heidelberg, Germany
[5] Heidelberg Univ, Inst Pathol, Heidelberg, Germany
[6] German Canc Res Ctr, Syst Biol Signal Transduct, Heidelberg, Germany
[7] Max Planck Inst Biochem, Cellular Dynam & Cell Patterning, Martinsried, Germany
[8] German Ctr Lung Res DZL Heidelberg, TLRC H, Heidelberg, Germany
[9] CancerSys Network LungSysII, Heidelberg, Germany
关键词
mitosis; non-small cell lung cancer; gene expression; prognostic marker; AURORA-A KINASE; SPINDLE FORMATION; PHOSPHORYLATION; ADENOCARCINOMA; HURP; SURVIVAL; ORGANIZATION; CHECKPOINT; MATURATION; INHIBITOR;
D O I
10.3892/ijo.2017.3834
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:365 / 372
页数:8
相关论文
共 40 条
[1]   MCAK-Independent Functions of ch-Tog/XMAP215 in Microtubule Plus-End Dynamics [J].
Barr, Alexis R. ;
Gergely, Fanni .
MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (23) :7199-7211
[2]   Structural basis of Aurora-A activation by TPX2 at the mitotic spindle [J].
Bayliss, R ;
Sardon, T ;
Vernos, I ;
Conti, E .
MOLECULAR CELL, 2003, 12 (04) :851-862
[3]   The 2004 World Health Organization classification of lung tumors [J].
Beasley, MB ;
Brambilla, E ;
Travis, WD .
SEMINARS IN ROENTGENOLOGY, 2005, 40 (02) :90-97
[4]   Phosphorylation by p34(cdc2) regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo [J].
Blangy, A ;
Lane, HA ;
dHerin, P ;
Harper, M ;
Kress, M ;
Nigg, EA .
CELL, 1995, 83 (07) :1159-1169
[5]   Cutoff Finder: A Comprehensive and Straightforward Web Application Enabling Rapid Biomarker Cutoff Optimization [J].
Budczies, Jan ;
Klauschen, Frederick ;
Sinn, Bruno V. ;
Gyoerffy, Balazs ;
Schmitt, Wolfgang D. ;
Darb-Esfahani, Silvia ;
Denkert, Carsten .
PLOS ONE, 2012, 7 (12)
[6]   The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments [J].
Bustin, Stephen A. ;
Benes, Vladimir ;
Garson, Jeremy A. ;
Hellemans, Jan ;
Huggett, Jim ;
Kubista, Mikael ;
Mueller, Reinhold ;
Nolan, Tania ;
Pfaffl, Michael W. ;
Shipley, Gregory L. ;
Vandesompele, Jo ;
Wittwer, Carl T. .
CLINICAL CHEMISTRY, 2009, 55 (04) :611-622
[7]   TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly [J].
Cassimeris, L ;
Morabito, J .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (04) :1580-1590
[8]  
Chen LD, 2015, INT J CLIN EXP MED, V8, P12161
[9]   Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies [J].
Chinn, Danielle C. ;
Holland, William S. ;
Mack, Philip C. .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2014, 140 (07) :1137-1149
[10]   Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study [J].
Cuzick, Jack ;
Swanson, Gregory P. ;
Fisher, Gabrielle ;
Brothman, Arthur R. ;
Berney, Daniel M. ;
Reid, Julia E. ;
Mesher, David ;
Speights, V. O. ;
Stankiewicz, Elzbieta ;
Foster, Christopher S. ;
Moller, Henrik ;
Scardino, Peter ;
Warren, Jorja D. ;
Park, Jimmy ;
Younus, Adib ;
Flake, Dart D., II ;
Wagner, Susanne ;
Gutin, Alexander ;
Lanchbury, Jerry S. ;
Stone, Steven .
LANCET ONCOLOGY, 2011, 12 (03) :245-255