Skip to main content
Top
Published in: Tumor Biology 9/2015

01-09-2015 | Research Article

Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer

Authors: Ruifang Sun, Zhigang Liu, Lumin Wang, Weidong Lv, Jia Liu, Caixia Ding, Yong Yuan, Guangyan Lei, Changfu Xu

Published in: Tumor Biology | Issue 9/2015

Login to get access

Abstract

Paclitaxel can exert therapeutic effects by interacting with microtubules. Stathmin and β-III-tubulin, which have impact on microtubule activity, are believed to be involved in the chemotherapy. The purpose of the present study was to evaluate the associations between stathmin and β-III-tubulin expression and treatment response and survivals in patients with non-small cell lung cancer (NSCLC). Two hundred thirty-eight patients who were treated by platinum-based chemotherapy were enrolled in this study, among them, 111 patients also received paclitaxel treatment. Formalin-fixed and paraffin-embedded tumor tissues were collected for messenger RNA (mRNA) and protein detection. We assessed the associations of the two molecules with treatment response and survival outcome. High level of stathmin exhibited poor response to chemotherapy (for mRNA, P = 0.041; for protein, P = 0.017). Overexpression of stathmin was associated with shorter overall survival (for mRNA, P = 0.012; for protein, P = 0.014) and progression-free survival (for mRNA, P = 0.039; for protein, P = 0.022). Of note, this association was only observed in patients who were treated by both platinum and paclitaxel. Similar effects were not observed for β-III-tubulin. The findings demonstrated that paclitaxel effect may be interfered with stathmin; overexpression of stathmin is a predictive marker for a worse prognosis in patients with NSCLC who were treated by both platinum and paclitaxel chemotherapy.
Literature
1.
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
go back to reference Williams CD, Gajra A, Ganti AK, Kelley MJ. Use and impact of adjuvant chemotherapy in patients with resected non-small cell lung cancer. Cancer. 2014;120:1939–47.CrossRefPubMed Williams CD, Gajra A, Ganti AK, Kelley MJ. Use and impact of adjuvant chemotherapy in patients with resected non-small cell lung cancer. Cancer. 2014;120:1939–47.CrossRefPubMed
4.
go back to reference Liu L, Zhao E, Li C, Huang L, Xiao L, Cheng L, et al. Trim28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer. Cancer Epidemiol. 2013;37:71–8.CrossRefPubMed Liu L, Zhao E, Li C, Huang L, Xiao L, Cheng L, et al. Trim28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer. Cancer Epidemiol. 2013;37:71–8.CrossRefPubMed
5.
go back to reference Inomata M, Hayashi R, Tokui K, Taka C, Okazawa S, Kambara K, et al. Usefulness of the palliative prognostic index in patients with lung cancer. Med Oncol. 2014;31:154.CrossRefPubMed Inomata M, Hayashi R, Tokui K, Taka C, Okazawa S, Kambara K, et al. Usefulness of the palliative prognostic index in patients with lung cancer. Med Oncol. 2014;31:154.CrossRefPubMed
6.
go back to reference Banna GL, Lipari H, Nicolosi M, Basile A, Fraggetta F, Vaglica M, et al. A three-drug induction chemotherapy with gemcitabine, carboplatin, and paclitaxel for stage III non-small cell lung cancer. Med Oncol. 2013;30:533.CrossRefPubMed Banna GL, Lipari H, Nicolosi M, Basile A, Fraggetta F, Vaglica M, et al. A three-drug induction chemotherapy with gemcitabine, carboplatin, and paclitaxel for stage III non-small cell lung cancer. Med Oncol. 2013;30:533.CrossRefPubMed
7.
go back to reference Jouveshomme S, Canoui-Poitrine F, Le Thuaut A, Bastuji-Garin S. Results of platinum-based chemotherapy in unselected performance status (PS) 2 patients with advanced non-small cell lung cancer: a cohort study. Med Oncol. 2013;30:544.CrossRefPubMed Jouveshomme S, Canoui-Poitrine F, Le Thuaut A, Bastuji-Garin S. Results of platinum-based chemotherapy in unselected performance status (PS) 2 patients with advanced non-small cell lung cancer: a cohort study. Med Oncol. 2013;30:544.CrossRefPubMed
8.
go back to reference Buonato JM, Lazzara MJ. ERK1/2 blockade prevents epithelial-mesenchymal transition in lung cancer cells and promotes their sensitivity to EGFR inhibition. Cancer Res. 2014;74:309–19.CrossRefPubMed Buonato JM, Lazzara MJ. ERK1/2 blockade prevents epithelial-mesenchymal transition in lung cancer cells and promotes their sensitivity to EGFR inhibition. Cancer Res. 2014;74:309–19.CrossRefPubMed
9.
go back to reference Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in caucasian EGFR mutation-positive nsclc patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110:55–62.CrossRefPubMed Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in caucasian EGFR mutation-positive nsclc patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110:55–62.CrossRefPubMed
11.
12.
go back to reference Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, et al. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC clinical trials group study BR29. Eur J Cancer. 2014;50:706–12.CrossRefPubMed Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, et al. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC clinical trials group study BR29. Eur J Cancer. 2014;50:706–12.CrossRefPubMed
13.
go back to reference Zhang HL, Ruan L, Zheng LM, Whyte D, Tzeng CM, Zhou XW. Association between class III beta-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer: a meta-analysis. Lung Cancer. 2012;77:9–15.CrossRefPubMed Zhang HL, Ruan L, Zheng LM, Whyte D, Tzeng CM, Zhou XW. Association between class III beta-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer: a meta-analysis. Lung Cancer. 2012;77:9–15.CrossRefPubMed
14.
go back to reference Xi W, Rui W, Fang L, Ke D, Ping G, Hui-Zhong Z. Expression of stathmin/op18 as a significant prognostic factor for cervical carcinoma patients. J Cancer Res Clin Oncol. 2009;135:837–46.CrossRefPubMed Xi W, Rui W, Fang L, Ke D, Ping G, Hui-Zhong Z. Expression of stathmin/op18 as a significant prognostic factor for cervical carcinoma patients. J Cancer Res Clin Oncol. 2009;135:837–46.CrossRefPubMed
15.
go back to reference Akhtar J, Wang Z, Yu C, Zhang ZP, Bi MM. Stmn-1 gene: a predictor of survival in stage IIA esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy? Ann Surg Oncol. 2014;21:315–21.CrossRefPubMed Akhtar J, Wang Z, Yu C, Zhang ZP, Bi MM. Stmn-1 gene: a predictor of survival in stage IIA esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy? Ann Surg Oncol. 2014;21:315–21.CrossRefPubMed
16.
go back to reference Belletti B, Baldassarre G. Stathmin: a protein with many tasks. New biomarker and potential target in cancer. Expert Opin Ther Targets. 2011;15:1249–66.CrossRefPubMed Belletti B, Baldassarre G. Stathmin: a protein with many tasks. New biomarker and potential target in cancer. Expert Opin Ther Targets. 2011;15:1249–66.CrossRefPubMed
17.
go back to reference Werner HM, Trovik J, Halle MK, Wik E, Akslen LA, Birkeland E, et al. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer. PLoS One. 2014;9:e90141.CrossRefPubMedPubMedCentral Werner HM, Trovik J, Halle MK, Wik E, Akslen LA, Birkeland E, et al. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer. PLoS One. 2014;9:e90141.CrossRefPubMedPubMedCentral
18.
go back to reference Phadke AP, Jay CM, Wang Z, Chen S, Liu S, Haddock C, et al. In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human stathmin 1 oncoprotein. DNA Cell Biol. 2011;30:715–26.CrossRefPubMed Phadke AP, Jay CM, Wang Z, Chen S, Liu S, Haddock C, et al. In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human stathmin 1 oncoprotein. DNA Cell Biol. 2011;30:715–26.CrossRefPubMed
19.
go back to reference Rana S, Maples PB, Senzer N, Nemunaitis J. Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 2008;8:1461–70.CrossRefPubMed Rana S, Maples PB, Senzer N, Nemunaitis J. Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 2008;8:1461–70.CrossRefPubMed
20.
go back to reference 20 Nie W, Xu MD, Gan L, Huang H, Xiu Q, Li B: Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer. Lab Invest 2014. 20 Nie W, Xu MD, Gan L, Huang H, Xiu Q, Li B: Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer. Lab Invest 2014.
21.
go back to reference Su D, Smith SM, Preti M, Schwartz P, Rutherford TJ, Menato G, et al. Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel. Cancer. 2009;115:2453–63.CrossRefPubMed Su D, Smith SM, Preti M, Schwartz P, Rutherford TJ, Menato G, et al. Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel. Cancer. 2009;115:2453–63.CrossRefPubMed
22.
go back to reference Chen G, Wang H, Gharib TG, Huang CC, Thomas DG, Shedden KA, et al. Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. Mol Cell Proteomics. 2003;2:107–16.CrossRefPubMed Chen G, Wang H, Gharib TG, Huang CC, Thomas DG, Shedden KA, et al. Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. Mol Cell Proteomics. 2003;2:107–16.CrossRefPubMed
23.
go back to reference Seve P, Isaac S, Tredan O, Souquet PJ, Pacheco Y, Perol M, et al. Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res. 2005;11:5481–6.CrossRefPubMed Seve P, Isaac S, Tredan O, Souquet PJ, Pacheco Y, Perol M, et al. Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res. 2005;11:5481–6.CrossRefPubMed
24.
go back to reference Rolfo C, Giovannetti E, Hong DS, Bivona T, Raez LE, Bronte G, et al. Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. Cancer Treat Rev. 2014;40:990–1004.CrossRefPubMed Rolfo C, Giovannetti E, Hong DS, Bivona T, Raez LE, Bronte G, et al. Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. Cancer Treat Rev. 2014;40:990–1004.CrossRefPubMed
25.
go back to reference Tsai CM, Chiu CH, Chang KT, Chen JT, Lai CL, Chen YM, et al. Gefitinib enhances cytotoxicities of antimicrotubule agents in non-small-cell lung cancer cells exhibiting no sensitizing epidermal growth factor receptor mutation. J Thorac Oncol. 2012;7:1218–27.CrossRefPubMed Tsai CM, Chiu CH, Chang KT, Chen JT, Lai CL, Chen YM, et al. Gefitinib enhances cytotoxicities of antimicrotubule agents in non-small-cell lung cancer cells exhibiting no sensitizing epidermal growth factor receptor mutation. J Thorac Oncol. 2012;7:1218–27.CrossRefPubMed
26.
go back to reference Han ZX, Wang HM, Jiang G, Du XP, Gao XY, Pei DS. Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2. Cancer Biother Radiopharm. 2013;28:398–405.CrossRefPubMed Han ZX, Wang HM, Jiang G, Du XP, Gao XY, Pei DS. Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2. Cancer Biother Radiopharm. 2013;28:398–405.CrossRefPubMed
27.
go back to reference Alli E, Bash-Babula J, Yang JM, Hait WN. Effect of stathmin on the sensitivity to antimicrotubule drugs in human breast cancer. Cancer Res. 2002;62:6864–9.PubMed Alli E, Bash-Babula J, Yang JM, Hait WN. Effect of stathmin on the sensitivity to antimicrotubule drugs in human breast cancer. Cancer Res. 2002;62:6864–9.PubMed
28.
go back to reference Alli E, Yang JM, Hait WN. Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene. 2007;26:1003–12.CrossRefPubMed Alli E, Yang JM, Hait WN. Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene. 2007;26:1003–12.CrossRefPubMed
29.
go back to reference Balachandran R, Welsh MJ, Day BW. Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells. Oncogene. 2003;22:8924–30.CrossRefPubMed Balachandran R, Welsh MJ, Day BW. Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells. Oncogene. 2003;22:8924–30.CrossRefPubMed
30.
go back to reference Mistry SJ, Bank A, Atweh GF. Synergistic antiangiogenic effects of stathmin inhibition and taxol exposure. Mol Cancer Res. 2007;5:773–82.CrossRefPubMed Mistry SJ, Bank A, Atweh GF. Synergistic antiangiogenic effects of stathmin inhibition and taxol exposure. Mol Cancer Res. 2007;5:773–82.CrossRefPubMed
31.
go back to reference George SL. Response rate as an endpoint in clinical trials. J Natl Cancer Inst. 2007;99:98–9. George SL. Response rate as an endpoint in clinical trials. J Natl Cancer Inst. 2007;99:98–9.
32.
go back to reference Jakobsen JN, Santoni-Rugiu E, Sorensen JB. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. Cancer Chemother Pharmacol. 2014;73:43–51.CrossRefPubMed Jakobsen JN, Santoni-Rugiu E, Sorensen JB. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. Cancer Chemother Pharmacol. 2014;73:43–51.CrossRefPubMed
33.
go back to reference Saura C, Tseng LM, Chan S, Chacko RT, Campone M, Manikhas A, et al. Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early stage breast cancer and evaluation of betaIII-tubulin expression as a predictive marker. Oncologist. 2013;18:787–94.CrossRefPubMedPubMedCentral Saura C, Tseng LM, Chan S, Chacko RT, Campone M, Manikhas A, et al. Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early stage breast cancer and evaluation of betaIII-tubulin expression as a predictive marker. Oncologist. 2013;18:787–94.CrossRefPubMedPubMedCentral
34.
go back to reference Vilmar AC, Santoni-Rugiu E, Sorensen JB. Class III beta-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial. Clin Cancer Res. 2011;17:5205–14.CrossRefPubMed Vilmar AC, Santoni-Rugiu E, Sorensen JB. Class III beta-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial. Clin Cancer Res. 2011;17:5205–14.CrossRefPubMed
Metadata
Title
Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer
Authors
Ruifang Sun
Zhigang Liu
Lumin Wang
Weidong Lv
Jia Liu
Caixia Ding
Yong Yuan
Guangyan Lei
Changfu Xu
Publication date
01-09-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3361-y

Other articles of this Issue 9/2015

Tumor Biology 9/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine