Graduate Institute of Oncology, National Taiwan University College of Medicine, 1, Sec. 1, Ren'ai Rd., Taipei 100, Taiwan.
Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan S. Rd., Taipei 100, Taiwan.
Cells. 2021 Jul 5;10(7):1698. doi: 10.3390/cells10071698.
The kinesin , a mitosis-associated protein, is overexpressed in many cancers. Here we explored the clinical significance of in hepatocellular carcinoma (HCC).
HCC tissues from surgical resection were collected. Total RNA was prepared from tumorous and nontumorous parts. expression levels were correlated with overall survival (OS) and disease-free survival (DFS). In vitro efficacy of LGI-147, a specific inhibitor, was tested in HCC cell lines. In vivo efficacy of inhibition was investigated in a xenograft model.
A total of 108 HCC samples were included. The patients were divided into three tertile groups with high, medium, and low expression levels. OS of patients with low expression was better than that of patients with medium and high expression (median, 155.6 vs. 75.3 vs. 57.7 months, = 0.002). DFS of patients with low expression was also better than that of patients with medium and high expression (median, 126.3 vs. 46.2 vs. 39.4 months, = 0.001). In multivariate analyses, the associations between expression and OS ( < 0.001) or DFS remained ( < 0.001). LGI-147 reduced cell growth via cell cycle arrest and apoptosis and induced accumulation of abnormal mitotic cells. In the xenograft model, the tumor growth rate under LGI-147 treatment was significantly slower than under the control.
High expression was associated with poor HCC prognosis. In vitro and in vivo evidence suggests that may be a reasonable therapeutic target for HCC.
驱动蛋白是一种有丝分裂相关蛋白，在许多癌症中过表达。在这里，我们探讨了在肝细胞癌（HCC）中的 表达的临床意义。
收集手术切除的 HCC 组织。从肿瘤和非肿瘤部分制备总 RNA。 表达水平与总生存（OS）和无病生存（DFS）相关。在 HCC 细胞系中测试了特异性 抑制剂 LGI-147 的体外疗效。在异种移植模型中研究了 抑制的体内疗效。
共纳入 108 例 HCC 样本。患者分为三组，表达水平高、中、低。低表达患者的 OS 优于中、高表达患者（中位数 155.6、75.3 和 57.7 个月， = 0.002）。低表达患者的 DFS 也优于中、高表达患者（中位数 126.3、46.2 和 39.4 个月， = 0.001）。多变量分析显示， 表达与 OS（ < 0.001）或 DFS 之间存在相关性（ < 0.001）。LGI-147 通过细胞周期停滞和凋亡减少细胞生长，并诱导异常有丝分裂细胞的积累。在异种移植模型中，LGI-147 治疗下的肿瘤生长速度明显慢于对照组。
高 表达与 HCC 预后不良相关。体外和体内证据表明， 可能是 HCC 的合理治疗靶点。
