TY - JOUR
T1 - AURKA, DLGAP5, TPX2, KIF11 and CKAP5
T2 - Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients
AU - Schneider, Marc A.
AU - Christopoulos, Petros
AU - Muley, Thomas
AU - Warth, Arne
AU - Klingmueller, Ursula
AU - Thomas, Michael
AU - Herth, Felix J.F.
AU - Dienemann, Hendrik
AU - Mueller, Nikola S.
AU - Theis, Fabian
AU - Meister, Michael
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
KW - Gene expression
KW - Mitosis
KW - Non-small cell lung cancer
KW - Prognostic marker genes
UR - http://www.scopus.com/inward/record.url?scp=85013040786&partnerID=8YFLogxK
U2 - 10.3892/ijo.2017.3834
DO - 10.3892/ijo.2017.3834
M3 - Article
C2 - 28101582
AN - SCOPUS:85013040786
SN - 1019-6439
VL - 50
SP - 365
EP - 372
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 2
ER -