Overexpression of Stathmin 1 correlates with poor prognosis and promotes cell migration and proliferation in oesophageal squamous cell carcinoma

Ni,Peng-Zhi; He,Jian-Zhong; Wu,Zhi-Yong; Ji,Xiang; Chen,Long-Qi; Xu,Xiu-E; Liao,Lian-Di; Wu,Jian-Yi; Li,En-Min; Xu,Li-Yan

doi:10.3892/or.2017.6039

Overexpression of Stathmin 1 correlates with poor prognosis and promotes cell migration and proliferation in oesophageal squamous cell carcinoma

Authors:
- Peng-Zhi Ni
- Jian-Zhong He
- Zhi-Yong Wu
- Xiang Ji
- Long-Qi Chen
- Xiu-E Xu
- Lian-Di Liao
- Jian-Yi Wu
- En-Min Li
- Li-Yan Xu
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Affiliations: Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Oncology Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong 515041, P.R. China
Published online on: October 17, 2017 https://doi.org/10.3892/or.2017.6039
Pages: 3608-3618

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Abstract

Stathmin 1 (STMN1) is a microtubule-regulated protein that plays an important role in tumour cell proliferation and migration. Overexpression of STMN1 is associated with clinicopathological characteristics in many human cancers. The aim of the present study was to investigate STMN1 expression, its correlation with clinicopathological characteristics, and its exact biological function in oesophageal squamous cell carcinoma (ESCC). STMN1 levels were measured in the ESCC tissue specimens of 276 patients by immunohistochemistry (IHC) to assess the prognostic efficacy of STMN1. IHC showed that patients with overexpression of STMN1 had a poorer prognosis compared with those with low expression, both in regards to 5-year overall survival (OS; 21.2 vs. 53.7%, P<0.001) and disease-free survival (DFS; 20.6 vs. 50.9%, P<0.001). STMN1 overexpression was associated with lower cell differentiation in tumour grade (correlation coefficient: 0.127, P=0.037). In multivariate analysis, STMN1 expression was found to be an independent prognostic factor for both OS (P<0.001; 95% CI, 1.555-2.970) and DFS (P=0.001; 95% CI, 1.978-2.444). Compared with the control, STMN1 downregulation significantly decreased cell migration, invasion and proliferation, whereas these were increased by STMN1 upregulation. STMN1 expression was significantly associated with prognosis and tumour differentiation in ESCC, indicating that STMN1 expression is an independent prognostic factor for ESCC and could be a potential biomarker. Regulating the expression of STMN1 could influence tumour cell motility, invasion and proliferation.

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1	Enzinger PC and Mayer RJ: Esophageal cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI
2	Kollarova H, Machova L, Horakova D, Janoutova G and Janout V: Epidemiology of esophageal cancer - an overview article. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 151:17–20. 2007. View Article : Google Scholar : PubMed/NCBI
3	Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI
4	Rubin CI and Atweh GF: The role of stathmin in the regulation of the cell cycle. J Cell Biochem. 93:242–250. 2004. View Article : Google Scholar : PubMed/NCBI
5	Tian FJ, Qin CM, Li XC, Wu F, Liu XR, Xu WM and Lin Y: Decreased stathmin-1 expression inhibits trophoblast proliferation and invasion and is associated with recurrent miscarriage. Am J Pathol. 185:2709–2721. 2015. View Article : Google Scholar : PubMed/NCBI
6	Machado-Neto JA, Saad STO and Traina F: Stathmin 1 in normal and malignant hematopoiesis. BMB Rep. 47:660–665. 2014. View Article : Google Scholar : PubMed/NCBI
7	Rana S, Maples PB, Senzer N and Nemunaitis J: Stathmin 1: A novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 8:1461–1470. 2008. View Article : Google Scholar : PubMed/NCBI
8	Wei SH, Lin F, Wang X, Gao P and Zhang HZ: Prognostic significance of stathmin expression in correlation with metastasis and clinicopathological characteristics in human ovarian carcinoma. Acta Histochem. 110:59–65. 2008. View Article : Google Scholar : PubMed/NCBI
9	Ghosh R, Gu G, Tillman E, Yuan J, Wang Y, Fazli L, Rennie PS and Kasper S: Increased expression and differential phosphorylation of stathmin may promote prostate cancer progression. Prostate. 67:1038–1052. 2007. View Article : Google Scholar : PubMed/NCBI
10	Baquero MT, Hanna JA, Neumeister V, Cheng H, Molinaro AM, Harris LN and Rimm DL: Stathmin expression and its relationship to microtubule-associated protein tau and outcome in breast cancer. Cancer. 118:4660–4669. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ma HL, Jin SF, Tao WJ, Zhang ML and Zhang ZY: Overexpression of stathmin/oncoprotein 18 correlates with poorer prognosis and interacts with p53 in oral squamous cell carcinoma. J Craniomaxillofac Surg. 44:1725–1732. 2016. View Article : Google Scholar : PubMed/NCBI
12	Gan L, Guo K, Li Y, Kang X, Sun L, Shu H and Liu Y: Upregulated expression of stathmin may be associated with hepatocarcinogenesis. Oncol Rep. 23:1037–1043. 2010.PubMed/NCBI
13	Zhang HZ, Gao P, Yan L and Lin F: Significance of stathmin gene overexpression in osteosarcoma cells. Ai Zheng. 23:493–496. 2004.(In Chinese). PubMed/NCBI
14	Sun R, Liu Z, Wang L, Lv W, Liu J, Ding C, Yuan Y, Lei G and Xu C: Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer. Tumour Biol. 36:7195–7204. 2015. View Article : Google Scholar : PubMed/NCBI
15	Nie W, Xu MD, Gan L, Huang H, Xiu Q and Li B: Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer. Lab Invest. 95:56–64. 2015. View Article : Google Scholar : PubMed/NCBI
16	Wang F, Wang LX, He W, Zhu LN, Zhao PR and Fan QX: Expression of stathmin in esophageal squamous cell carcinoma and its biological significance. Nan Fang Yi Ke Da Xue Xue Bao. 30:1552–1557. 2010.(In Chinese). PubMed/NCBI
17	Akhtar J, Wang Z, Jiang WP, Bi MM and Zhang ZP: Stathmin overexpression identifies high risk for lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma patients. J Gastroenterol Hepatol. 29:944–950. 2014. View Article : Google Scholar : PubMed/NCBI
18	Rice TW, Blackstone EH and Rusch VW: 7th edition of the AJCC Cancer Staging Manual: Esophagus and esophagogastric junction. Ann Surg Oncol. 17:1721–1724. 2010. View Article : Google Scholar : PubMed/NCBI
19	Fléjou JF: WHO Classification of Digestive Tumors: 4th edition. Ann Pathol. 31 Suppl 5:S27–S31. 2011.(In French). View Article : Google Scholar : PubMed/NCBI
20	Xie JJ, Xu LY, Wu ZY, Zhao Q, Xu XE, Wu JY, Huang Q and Li EM: Prognostic implication of ezrin expression in esophageal squamous cell carcinoma. J Surg Oncol. 104:538–543. 2011. View Article : Google Scholar : PubMed/NCBI
21	Sun LL, Holowatyj A, Xu XE, Wu JY, Wu ZY, Shen JH, Wang SH, Li EM, Yang ZQ and Xu LY: Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma. Am J Cancer Res. 3:509–517. 2013.PubMed/NCBI
22	Xie JJ, Zhang FR, Tao LH, Lü Z, Xu XE, Jian S, Xu LY and Li EM: Expression of ezrin in human embryonic, fetal, and normal adult tissues. J Histochem Cytochem. 59:1001–1008. 2011. View Article : Google Scholar : PubMed/NCBI
23	Xie JJ, Xu LY, Wu JY, Shen ZY, Zhao Q, Du ZP, Lv Z, Gu W, Pan F, Xu XE, et al: Involvement of CYR61 and CTGF in the fascin-mediated proliferation and invasiveness of esophageal squamous cell carcinomas cells. Am J Pathol. 176:939–951. 2010. View Article : Google Scholar : PubMed/NCBI
24	Kuang XY, Chen L, Zhang ZJ, Liu YR, Zheng YZ, Ling H, Qiao F, Li S, Hu X and Shao ZM: Stathmin and phospho-stathmin protein signature is associated with survival outcomes of breast cancer patients. Oncotarget. 6:22227–22238. 2015. View Article : Google Scholar : PubMed/NCBI
25	Lu Y, Liu C, Cheng H, Xu Y, Jiang J, Xu J, Long J, Liu L and Yu X: Stathmin, interacting with Nf-κB, promotes tumor growth and predicts poor prognosis of pancreatic cancer. Curr Mol Med. 14:328–339. 2014. View Article : Google Scholar : PubMed/NCBI
26	Ke B, Wu LL, Liu N, Zhang RP, Wang CL and Liang H: Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer. Tumour Biol. 34:3137–3145. 2013. View Article : Google Scholar : PubMed/NCBI
27	Hsieh SY, Huang SF, Yu MC, Yeh TS, Chen TC, Lin YJ, Chang CJ, Sung CM, Lee YL and Hsu CY: Stathmin1 overexpression associated with polyploidy, tumor-cell invasion, early recurrence, and poor prognosis in human hepatoma. Mol Carcinog. 49:476–487. 2010.PubMed/NCBI
28	Sherbet GV and Cajone F: Stathmin in cell proliferation and cancer progression. Cancer Genomics Proteomics. 2:227–237. 2005.
29	Li X, Wang L, Li T, You B, Shan Y, Shi S, Qian L and Cao X: STMN1 overexpression correlates with biological behavior in human cutaneous squamous cell carcinoma. Pathol Res Pract. 211:816–823. 2015. View Article : Google Scholar : PubMed/NCBI
30	Li J, Hu G, Kong F, Wu K, Song K, He J and Sun W: Elevated STMN1 expression correlates with poor prognosis in patients with pancreatic ductal adenocarcinoma. Pathol Oncol Res. 21:1013–1020. 2015. View Article : Google Scholar : PubMed/NCBI
31	Liu F, Sun YL, Xu Y, Liu F, Wang LS and Zhao XH: Expression and phosphorylation of stathmin correlate with cell migration in esophageal squamous cell carcinoma. Oncol Rep. 29:419–424. 2013. View Article : Google Scholar : PubMed/NCBI
32	Chen Y, Zhang Q, Ding C, Zhang X, Qiu X and Zhang Z: Stathmin1 overexpression in hypopharyngeal squamous cell carcinoma: A new promoter in FaDu cell proliferation and migration. Int J Oncol. 50:31–40. 2017. View Article : Google Scholar : PubMed/NCBI