Stathmin1 Overexpression Associated With Polyploidy, Tumor-Cell Invasion, Early Recurrence, and Poor Prognosis in Human Hepatoma
Stathmin1 Overexpression Associated With Polyploidy, Tumor-Cell Invasion, Early Recurrence, and Poor Prognosis in Human Hepatoma
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DOI：
10.1002/mc.20627
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发表时间：
2010-05-01
影响因子：
4.6
通讯作者：
Hsu, Chih-Yun
中科院分区：
文献类型：
--
作者：
Hsieh, Sen-Yung;Huang, Shiu-Feng;Hsu, Chih-Yun
肝细胞癌（HCC）频繁的肝内转移导致早期复发和预后不良。我们最近发现stathmin 1（STMN 1）在人HCC中过表达。本研究旨在阐明STMN 1在HCC中过表达的临床和生物学意义。采用定量逆转录-聚合酶链反应和免疫印迹法检测58对HCC患者的HCC和癌旁肝组织中STMN 1的表达，并以正常肝组织作为对照。通过Kaplan-Meier累积生存率和考克斯回归分析研究STMN 1过表达与肿瘤复发和预后的关系。STMN 1在细胞周期，细胞运动性和侵袭中的作用通过体外测定来确定。STMN 1在肝癌中的过表达与局部浸润（P=0.031）、早期复发（P=0.002）和预后不良（P=0.005）密切相关，并且是肿瘤复发的独立指标（P=0.0045）。STMN 1过表达进一步鉴定了在具有早期肿瘤阶段（T1）或中间组织学分级（G2和G3）的HCC患者中具有较高肿瘤复发和较差预后的HCC患者亚组，这两者都代表了接受原发性根治性肝切除术的大多数HCC患者。通过RNA干扰沉默STMN 1表达抑制侵袭活性，而STMN 1的异位表达增强细胞侵袭并引起细胞的多倍性。STMN 1过表达可预测肝癌早期复发和不良预后，尤其是在肝癌早期。STMN 1的过表达促进了多倍性形成、肿瘤细胞侵袭和肝内转移，表明STMN 1可以成为人类肝癌抗癌治疗的靶点。(C)2010 Wiley-Liss，Inc.
Frequent intrahepatic metastasis causes early tumor recurrence and dismaying prognosis of human hepatocellular carcinoma (HCC). We recently identified overexpression of stathmin1 (STMN1) in human HCC. This study was designed to elucidate the clinical and biological significance of overexpression of STMN1 in HCC. Expression of STMN1 was conducted by quantitative reverse transcription-polymerase chain reaction and immunoblotting assays on 58 pairs of HCC and para-tumor liver tissues from patients with HCC along with normal liver tissues as the controls. Association of STMN1 overexpression with tumor recurrence and prognosis was investigated by Kaplan-Meier cumulative survival and Cox Regression analyses. Roles of STMN1 in cell cycle, cell motility, and invasion were determined by in vitro assays. STMN1 overexpression in hepatoma was strongly associated with local invasion (P=0.031), early recurrence (P=0.002), and poor prognosis (P=0.005), and was an independent indicator for tumor recurrence (P=0.0045). STMN1 overexpression further identified subgroups of HCC patients with higher tumor recurrence and worse prognosis among HCC patients with early tumor stage (T1) or intermediate histological grades (G2 and G3), both of whom represent the majority of HCC patients receiving primary curative hepatectomy. Silencing STMN1 expression via RNA interference suppressed invasion activity, while ectopic expression of STMN1 enhanced cell invasion and caused polyploidy of cells. In conclusion, STMN1 overexpression could predict early tumor recurrence and poor prognosis, particularly at early stage of hepatoma. Overexpression of STMN1 promoted polyploidy formation, tumor-cell invasion, and intrahepatic metastasis, suggesting that STMN1 can be a target for anti-cancer therapy of human hepatoma. (C) 2010 Wiley-Liss, Inc.