Ke Bin, Guo Xiao-Fan, Li Ning, Wu Liang-Liang, Li Bin, Zhang Ru-Peng, Liang Han
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
Mol Clin Oncol. 2019 Feb;10(2):214-222. doi: 10.3892/mco.2018.1774. Epub 2018 Nov 26.
In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.
在我们之前的研究中，已证实Stathmin1（STMN1）在胃癌（GC）中过表达，且其高表达水平与肿瘤侵袭和转移相关。上皮-间质转化（EMT）也已被证明在GC侵袭和转移中起关键作用。某些研究表明，STMN1可能在EMT过程中发挥重要作用。然而，STMN1表达与EMT相关标志物以及GC患者临床病理特征之间的关联仍不清楚。本研究的目的是探讨STMN1和EMT相关标志物在GC中的临床病理意义及预后价值。通过免疫组织化学分析GC组织及癌旁非肿瘤组织中STMN1以及EMT相关蛋白E-钙黏蛋白（E-Cad）和波形蛋白（VIM）的表达。分析这些标志物表达与临床病理参数之间的关联。在GC细胞系BGC-803和SGC-7901中研究STMN1表达与EMT相关标志物之间的关联。结果显示，167例GC组织中有63.5%表达STMN1，这一比例显著高于癌旁非肿瘤组织中的比例（P = 0.003）。在GC组织中，STMN1表达与VIM水平呈正相关（P = 0.001），与E-Cad水平呈负相关（P = 0.022）。STMN1表达与劳伦分型、浸润深度、淋巴结转移及病理肿瘤-淋巴结-转移（pTNM）分期相关（P < 0.05）。在单因素分析中，E-Cad高表达是总生存的阳性预后指标，而STMN1和VIM高表达是阴性指标。COX多因素回归分析表明，pTNM分期[风险比（HR）1.912，95%置信区间（CI）：1.282 - 2.851，P = 0.001]和E-Cad表达（HR 0.403，95% CI：0.249 - 0.650，P = 0.000）是独立的预后因素。还发现，通过降低GC细胞中STMN1水平，E-Cad表达水平下降，而VIM表达水平升高。本研究结果表明，STMN1的异常表达可能通过EMT促进GC的肿瘤进展。
