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高 STMN1 表达与肺鳞状细胞癌的癌症进展和化疗耐药相关。

High STMN1 Expression is Associated with Cancer Progression and Chemo-Resistance in Lung Squamous Cell Carcinoma.

机构信息

Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.

Research Program for Omics-Based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Gunma, Japan.

出版信息

Ann Surg Oncol. 2017 Dec;24(13):4017-4024. doi: 10.1245/s10434-017-6083-0. Epub 2017 Sep 20.

DOI:10.1245/s10434-017-6083-0
PMID:28933054
Abstract

BACKGROUND

Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis.

METHODS

Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity.

RESULTS

The cytoplasmic STMN1 expression in LSCC was higher than in normal tissues. The high expression was significantly associated with vascular invasion (P = 0.0477) and poor prognosis. In addition, the proliferating and invasive abilities were decreased, and the apoptosis ability and paclitaxel sensitivity were increased in STMN1-suppressed LSCC cells compared with control cells.

CONCLUSION

The results suggest that STMN1 is a prognostic factor that also is associated with caner progression and chemo-resistance. Therefore, STMN1 could be a predictor for poor prognosis and a potential therapeutic target in LSCC.

摘要

背景

STMN1(基因符号:STMN1)作为一种微管不稳定蛋白,调节微管的动态、细胞周期进程和对紫杉烷类药物的化疗耐药性。它在各种人类癌症中高度表达,并参与癌症进展和预后不良。

方法

使用来自 186 例肺鳞癌(LSCC)患者的 FFPE 组织切片通过免疫组织化学检测 STMN1 的表达。对 STMN1 小干扰 RNA(siRNA)转染的 LSCC 细胞系进行 STMN1 抑制分析,以确定增殖、侵袭和凋亡能力以及紫杉醇敏感性的变化。

结果

LSCC 中的细胞质 STMN1 表达高于正常组织。高表达与血管侵犯显著相关(P=0.0477)和预后不良。此外,与对照细胞相比,STMN1 抑制的 LSCC 细胞的增殖和侵袭能力降低,凋亡能力和紫杉醇敏感性增加。

结论

结果表明 STMN1 是一个预后因素,也与癌症进展和化疗耐药性相关。因此,STMN1 可能是 LSCC 预后不良的预测因子和潜在的治疗靶点。

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