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STMN1水平升高与胃癌患者的化疗耐药及不良预后相关。

High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.

作者信息

Bai Tuya, Yokobori Takehiko, Altan Bolag, Ide Munenori, Mochiki Erito, Yanai Mitsuhiro, Kimura Akiharu, Kogure Norimichi, Yanoma Toru, Suzuki Masaki, Bao Pinjie, Kaira Kyoichi, Asao Takayuki, Katayama Ayaka, Handa Tadashi, Gombodorj Navchaa, Nishiyama Masahiko, Oyama Tetsunari, Ogata Kyoichi, Kuwano Hiroyuki

机构信息

Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.

Research Program for Omics-based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma 3718511, Japan.

出版信息

Br J Cancer. 2017 Apr 25;116(9):1177-1185. doi: 10.1038/bjc.2017.76. Epub 2017 Mar 23.

Abstract

BACKGROUND

Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases.

METHODS

Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines.

RESULTS

Multivariate and Kaplan-Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis.

CONCLUSIONS

STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.

摘要

背景

Stathmin1(STMN1)是一种胞质磷蛋白,可调节细胞微管动力学,已知具有致癌活性。尽管有多项报道,但由于缺乏对高转移病例的分析,其在胃癌(GC)中的作用仍不清楚。本研究旨在探讨STMN1作为GC患者(包括无法手术的病例)对紫杉醇治疗反应的预后和预测指标。

方法

对可手术(n = 95)和不可手术的GC(n = 61)样本进行STMN1的免疫组织化学分析。使用GC细胞系通过敲低实验证实了STMN1在癌细胞增殖和对微管靶向药物紫杉醇的敏感性中的作用。

结果

多变量分析和Kaplan-Meier分析表明,高STMN1预示着两组患者的预后不良。在可手术队列中,STMN1表达与癌症治愈率、复发和辅助治疗耐药性相关。在不可手术的病例中观察到与紫杉醇耐药性相关。在GC细胞系中敲低STMN1可抑制增殖,并通过增强凋亡使细胞对紫杉醇敏感。

结论

STMN1可能是GC中紫杉醇敏感性和预后不良的生物标志物,并且可能是转移性GC的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7609/5418450/105f2b0191be/bjc201776f1.jpg

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