Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma.
Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma.
复制标题
FORKHEAD BOX M1（FOXM1）表达和FOXM1抑制在血管肉瘤中的抗肿瘤作用的预后意义。
DOI：
10.7150/jca.14461
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发表时间：
2016
影响因子：
3.9
通讯作者：
Oda Y
中科院分区：
文献类型：
--
作者：
Ito T;Kohashi K;Yamada Y;Iwasaki T;Maekawa A;Kuda M;Hoshina D;Abe R;Furue M;Oda Y
背景：血管肉瘤的预后很差，需要一种新的治疗方法。本研究的目的是研究Forkhead box M1（FOXM 1）的预后意义，FOXM 1是一种调节细胞周期进程和肿瘤进展中各种关键过程的转录因子，及其作为新治疗靶点的潜力。研究方法：我们研究了125例血管肉瘤临床样本（94例原发性病变和31例转移性病变，94例患者）和人血管肉瘤细胞系（HAMON），采用免疫组化染色和分子生物学方法。FOXM 1在血管肉瘤中的表达也与Kaposi肉瘤（n = 13）、上皮样血管内皮瘤（n = 13）和良性血管瘤（n = 10）进行了比较。结果如下：FOXM 1过表达的血管肉瘤患者的生存率（疾病特异性生存率[DSS]和无事件生存率[EFS]）明显短于其他患者（5年DSS，23.5% vs. 47.1%，P = 0.013; 5年EFS，5.5% vs. 28.7%，P = 0.004）。在考克斯多变量分析中，FOXM 1过表达也是DSS和EFS的独立预后因素（分别为风险比[HR] 2.84，95%置信区间[CI] 1.10-5.81，P = 0.039; HR 4.16，95%CI 2.03-8.67，P = 0.0001）。使用小干扰RNA和特异性抑制剂（硫链丝菌素）抑制FOXM 1抑制血管肉瘤细胞系的细胞增殖。此外，FOXM 1抑制提高了体外对多西他赛的化疗敏感性。结论：FOXM 1抑制可能是血管肉瘤的一种潜在治疗选择。
Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.