Prognostic significance of integrin-linked kinase1 overexpression in astrocytoma

被引:16
作者
Li, Jun [2 ,3 ]
Zhang, Heng [4 ]
Wu, Jueheng [1 ,3 ]
Guan, Hongyu [1 ,3 ]
Yuan, Jie [2 ,3 ]
Huang, Zhengsong [4 ]
Li, Mengfeng [1 ,3 ]
机构
[1] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Microbiol, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biochem, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurosurg, Guangzhou 510080, Guangdong, Peoples R China
关键词
ILK1; astrocytoma; prognosis; biomarker; AP-1 TRANSCRIPTION FACTOR; GLYCOGEN-SYNTHASE KINASE; POOR PATIENT SURVIVAL; CELL LUNG-CANCER; INCREASED EXPRESSION; UP-REGULATION; ILK; INHIBITION; GLIOBLASTOMA; PROGRESSION;
D O I
10.1002/ijc.24824
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Integrin-linked kinase 1 (ILK1), a member of the serine/threonine kinases, has been demonstrated to be associated with numerous biological and pathological processes. However, the clinical and functional significance of ILK1 expression has not been characterized previously in human astrocytoma. In this study, we found that ILK1 was overexpressed, at both mRNA and protein levels, in astrocytoma cell lines as compared with normal human astrocytes. The ILK1 mRNA and protein were significantly increased up to 5.6-fold and 10.1-fold, respectively, in primary astrocytoma in comparison with the paired adjacent noncancerous brain tissues obtained from the same patient. Furthermore, immunohistochemical analysis revealed that ILK1 protein was positive in 208 of 228 (91.2%) paraffin-embedded archival astrocytoma specimens. Statistical analysis suggested that the upregulation of ILK1 was significantly correlated with the histological grading of astrocytoma (P = 0.000), and that patients with high ILK1 level exhibited shorter survival time (p < 0.001). Multivariate analysis revealed that ILK1 upregulation might be an independent prognostic indicator for the survival of patients with astrocytoma. Taken together, our results suggest that ILK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease.
引用
收藏
页码:1436 / 1444
页数:9
相关论文
共 34 条
[1]  
Abboud ER, 2007, INT J ONCOL, V30, P113
[2]   Cell-free 59 kDa immunoreactive integrin-linked kinase: A novel marker for ovarian carcinoma [J].
Ahmed, N ;
Oliva, K ;
Rice, GE ;
Quinn, MA .
CLINICAL CANCER RESEARCH, 2004, 10 (07) :2415-2420
[3]  
Dai DL, 2003, CLIN CANCER RES, V9, P4409
[4]   Medical progress: Brain tumors [J].
DeAngelis, LM .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (02) :114-123
[5]   Cell-substrate interactions and signaling through ILK [J].
Dedhar, S .
CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) :250-256
[6]   Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase [J].
Delcommenne, M ;
Tan, C ;
Gray, V ;
Rue, L ;
Woodgett, J ;
Dedhar, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (19) :11211-11216
[7]  
Deorah Sundeep, 2006, Neurosurg Focus, V20, pE1, DOI 10.3171/foc.2006.20.4.E1
[8]   Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth [J].
Edwards, LA ;
Thiessen, B ;
Dragowska, WH ;
Daynard, T ;
Bally, MB ;
Dedhar, S .
ONCOGENE, 2005, 24 (22) :3596-3605
[9]   Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells [J].
Edwards, LA ;
Verreault, M ;
Thiessen, B ;
Dragowska, WH ;
Hu, YP ;
Yeung, JHF ;
Dedhar, S ;
Bally, MB .
MOLECULAR CANCER THERAPEUTICS, 2006, 5 (03) :645-654
[10]   Suppression of VEGF secretion and changes in glioblastoma multiforme microenvironment by inhibition of Integrin-linked kinase (ILK) [J].
Edwards, Lincoln A. ;
Woo, Janet ;
Huxham, Lynsey A. ;
Verreault, Maite ;
Dragowska, Wieslawa H. ;
Chiu, Gigi ;
Rajput, Ashish ;
Kyle, Alastair H. ;
Kalra, Jessica ;
Yapp, Donald ;
Yan, Hong ;
Minchinton, Andrew I. ;
Huntsman, David ;
Daynard, Tim ;
Waterhouse, Dawn N. ;
Thiessen, B. ;
Dedhar, Shoukat ;
Bally, Marcel B. .
MOLECULAR CANCER THERAPEUTICS, 2008, 7 (01) :59-70