KIF20A expression as a prognostic indicator and its possible involvement in the proliferation of ovarian clear‑cell carcinoma cells.

KIF20A expression as a prognostic indicator and its possible involvement in the proliferation of ovarian clear‑cell carcinoma cells.
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DOI:
10.3892/or.2018.6401
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发表时间:
2018-07
期刊:
影响因子:
4.2
通讯作者:
Kajiyama H
Kajiyama H
中科院分区:
医学3区
文献类型:
--
作者:
Kawai Y;Shibata K;Sakata J;Suzuki S;Utsumi F;Niimi K;Sekiya R;Senga T;Kikkawa F;Kajiyama H

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驱动蛋白家族成员20 A(KIF 20 A)参与胞质分裂和细胞内转运,最近已报道在几种恶性肿瘤中上调,并且可能有助于化疗抗性。我们检测了KIF 20 A在卵巢透明细胞癌(CCC)中的分布和表达,以阐明其临床意义和分子机制。用KIF 20 A抗体对来自卵巢CCC组织的石蜡切片(N=43)进行免疫染色,并半定量地评估染色强度。此外,我们研究了沉默KIF 20 A是否有助于使用CCC细胞的增殖抑制潜力。在观察期间,18例患者(41.9%)复发。中位复发时间为11.5个月。KIF 20 A高表达组患者的无进展生存期(PFS)和总生存期(OS)均低于低表达组(分别为P=0.0443和P=0.0478)。在多变量分析中,KIF 20 A表达也是PFS的显著独立指标和OS的略微显著指标[PFS:HR(高vs.低),5.488; 95% CI,1.410-24.772(P=0.0136); OS:HR,2.835; 95% CI,0.854-11.035,(P=0.0897)]。在体外研究中,卵巢CCC细胞增殖显著降低KIF 20 A沉默或在CCC细胞中存在KIF 20 A抑制剂。与对照细胞相比,si-KIF 20 A转染的CCC细胞更频繁地观察到细胞周期G2/M期阻滞和更高的凋亡诱导分数。虽然目前的研究是初步的,但这些数据表明KIF 20 A可能参与CCC的增殖,这表明靶向该分子可能有助于逆转恶性潜能,从而影响CCC患者的肿瘤学结局。
Kinesin family member 20A (KIF20A), which is involved in cytokinesis and intracellular transportation, has been recently reported to be upregulated in several malignancies and may contribute to chemotherapeutic resistance. We examined the distribution and expression of KIF20A in clear-cell carcinoma (CCC) of the ovary to elucidate its clinical significance and molecular mechanism. Paraffin sections from ovarian CCC tissues (N=43) were immunostained with KIF20A antibody, and the staining intensities were semi-quantitatively evaluated. Furthermore, we investigated whether silencing of KIF20A contributes to the proliferation-inhibitory potential using CCC cells. During the observational period, 18 patients (41.9%) developed recurrence. The median time to recurrence was 11.5 months. Patients in the high KIF20A expression group showed poorer progression-free survival (PFS) and overall survival (OS) than those in the low expression group (P=0.0443 and P=0.0478, respectively). In multivariable analyses, KIF20A expression was also a significantly independent indicator of PFS and a marginally significant indicator of OS [PFS: HR (high vs. low), 5.488; 95% CI, 1.410–24.772 (P=0.0136); OS: HR, 2.835; 95% CI, 0.854–11.035, (P=0.0897)]. In in vitro studies, the ovarian CCC cell proliferation was significantly decreased by KIF20A silencing or in the presence of KIF20A inhibitor in CCC cells. Cell cycle G2/M arrest and a higher apoptosis-induced fraction were more frequently observed in si-KIF20A-transfected CCC cells than in the control cells. Although the present study was preliminary, these data indicate the possible involvement of KIF20A in the proliferation of CCC, suggesting that targeting this molecule may contribute to reversing the malignant potential consequently affecting the oncologic outcome of CCC patients.
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发表时间: 2003-04-10
期刊: ONCOGENE
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期刊: ANNALS OF ONCOLOGY
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