Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer

被引:65
作者
Nie, Wei [1 ]
Xu, Mi-die [2 ,3 ,4 ]
Gan, Lu [3 ,5 ]
Huang, Hai [6 ]
Xiu, Qingyu [6 ]
Li, Bing [6 ]
机构
[1] PLA, Hosp 425, Dept Internal Med, Sanya, Peoples R China
[2] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai 200433, Peoples R China
[3] Fudan Univ, Shanghai Canc Ctr, Dept Oncol, Shanghai 200433, Peoples R China
[4] Fudan Univ, Inst Pathol, Shanghai 200433, Peoples R China
[5] Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200433, Peoples R China
[6] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Resp Med, Shanghai 200003, Peoples R China
关键词
TUMOR PROGRESSION; EARLY RECURRENCE; GASTRIC-CANCER; CARCINOMA; PROTEIN; CLASSIFICATION; PROLIFERATION; EXPRESSION; MUTATION; TARGET;
D O I
10.1038/labinvest.2014.124
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (P < 0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (P < 0.001), large tumor size (P = 0.022), advanced N stage (P = 0.033), and advanced TNM stage (P < 0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95% CI 1.320-3.825, P = 0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.
引用
收藏
页码:56 / 64
页数:9
相关论文
共 20 条
[1]   ASSOCIATION OF P53 PROTEIN EXPRESSION WITH TUMOR-CELL PROLIFERATION RATE AND CLINICAL OUTCOME IN NODE-NEGATIVE BREAST-CANCER [J].
ALLRED, DC ;
CLARK, GM ;
ELLEDGE, R ;
FUQUA, SAW ;
BROWN, RW ;
CHAMNESS, GC ;
OSBORNE, CK ;
MCGUIRE, WL .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (03) :200-206
[2]   Stathmin: a protein with many tasks. New biomarker and potential target in cancer [J].
Belletti, Barbara ;
Baldassarre, Gustavo .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2011, 15 (11) :1249-1266
[3]   Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules [J].
Belmont, LD ;
Mitchison, TJ .
CELL, 1996, 84 (04) :623-631
[4]   The new World Health Organization classification of lung tumours [J].
Brambilla, E ;
Travis, WD ;
Colby, TV ;
Corrin, B ;
Shimosato, Y .
EUROPEAN RESPIRATORY JOURNAL, 2001, 18 (06) :1059-1068
[5]   Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas [J].
Chen, G ;
Wang, H ;
Gharib, TG ;
Huang, CC ;
Thomas, DG ;
Shedden, KA ;
Kuick, R ;
Taylor, JMG ;
Kardia, SLR ;
Misek, DE ;
Giordano, TJ ;
Iannettoni, MD ;
Orringer, MB ;
Hanash, SM ;
Beer, DG .
MOLECULAR & CELLULAR PROTEOMICS, 2003, 2 (02) :107-116
[6]   The IASLC lung cancer staging project: Proposals for the revision of he TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours [J].
Goldstraw, Peter ;
Crowley, John ;
Chansky, Kari ;
Giroux, Dorothy J. ;
Groome, Patti A. ;
Rami-Porta, Ramon ;
Postmus, Pieter E. ;
Rusch, Valerie ;
Sobin, Leslie .
JOURNAL OF THORACIC ONCOLOGY, 2007, 2 (08) :706-714
[7]   Stathmin1 Overexpression Associated With Polyploidy, Tumor-Cell Invasion, Early Recurrence, and Poor Prognosis in Human Hepatoma [J].
Hsieh, Sen-Yung ;
Huang, Shiu-Feng ;
Yu, Ming-Chin ;
Yeh, Ta-Sen ;
Chen, Tse-Chin ;
Lin, Yu-Jr ;
Chang, Chee-Jen ;
Sung, Chang-Mung ;
Lee, Yun-Lin ;
Hsu, Chih-Yun .
MOLECULAR CARCINOGENESIS, 2010, 49 (05) :476-487
[8]   Overexpression of stathmin 1 confers an independent prognostic indicator in nasopharyngeal carcinoma [J].
Hsu, Han-Ping ;
Li, Chien-Feng ;
Lee, Sung-Wei ;
Wu, Wen-Ren ;
Chen, Tzu-Ju ;
Chang, Kwang-Yu ;
Liang, Shih-Shin ;
Tsai, Chia-Jung ;
Shiue, Yow-Ling .
TUMOR BIOLOGY, 2014, 35 (03) :2619-2629
[9]   Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells [J].
Jeon, T-Y ;
Han, M-E ;
Lee, Y-W ;
Lee, Y-S ;
Kim, G-H ;
Song, G-A ;
Hur, G-Y ;
Kim, J-Y ;
Kim, H-J ;
Yoon, S. ;
Baek, S-Y ;
Kim, B-S ;
Kim, J-B ;
Oh, S-O .
BRITISH JOURNAL OF CANCER, 2010, 102 (04) :710-718
[10]   Correlation between microtubule-associated gene expression and chemosensitivity of patients with stage II non-small cell lung cancer [J].
Jiang, Hong ;
Yu, Xin-Ming ;
Zhou, Xing-Ming ;
Wang, Xiao-Hong ;
Su, Dan .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2013, 5 (05) :1506-1510