High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.
High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.
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DOI：
10.1038/bjc.2017.76
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发表时间：
2017-04-25
影响因子：
8.8
通讯作者：
Kuwano H
中科院分区：
文献类型：
--
作者：
Bai T;Yokobori T;Altan B;Ide M;Mochiki E;Yanai M;Kimura A;Kogure N;Yanoma T;Suzuki M;Bao P;Kaira K;Asao T;Katayama A;Handa T;Gombodorj N;Nishiyama M;Oyama T;Ogata K;Kuwano H
Stathmin 1（STMN 1）是一种调节细胞微管动力学的胞质磷蛋白，已知具有致癌活性。尽管有一些报道，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。本研究旨在研究STMN 1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。对可手术（n=95）和不可手术的GC（n=61）样本进行STMN 1的免疫组织化学分析。STMN 1在癌细胞增殖和对微管靶向药物紫杉醇敏感性中的作用通过使用GC细胞系的敲除实验得到证实。多变量和Kaplan-Meier分析表明，高STMN 1是两组预后不良的预测因素。在可手术队列中，STMN 1表达与癌症可治愈性、复发和对辅助治疗的抵抗相关。在不能手术的病例中观察到与紫杉醇耐药的相关性。在GC细胞系中敲低STMN 1抑制增殖，并通过增强凋亡使细胞对紫杉醇敏感。STMN 1可能是胃癌对紫杉醇敏感和预后不良的生物标志物，并可能成为转移性胃癌的新的治疗靶点。
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. 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. 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. STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.