Koike Yuhki, Yin Chengzeng, Sato Yuki, Nagano Yuka, Yamamoto Akira, Kitajima Takahito, Shimura Tadanobu, Kawamura Mikio, Matsushita Kohei, Okugawa Yoshinaga, Amano Keishiro, Otake Kohei, Okita Yoshiki, Ohi Masaki, Inoue Mikihiro, Uchida Keiichi, Hirayama Masahiro, Toiyama Yuji
Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Department of Genomic Medicine, Mie University Hospital, Tsu, Mie 514-8507, Japan.
Oncol Lett. 2022 Apr;23(4):136. doi: 10.3892/ol.2022.13256. Epub 2022 Feb 28.
Targeting protein for kinesin-like protein 2 (TPX2) is upregulated in various tumors, and several studies have demonstrated the role of TPX2 as a prognostic marker in cancer. However, the function of TPX2 in neuroblastoma (NB) has not been completely elucidated. In the present study, the clinical significance and functional role of TPX2 in NB was investigated. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-NB dataset was used. A total of 43 patients with NB were enrolled in the present study as the validation set. After evaluating the prognostic role of TPX2, the combined predictive effect of TPX2 and MYCN proto-oncogene bHLH transcription factor (MYCN) gene amplification was assessed. Double immunofluorescence staining for TPX2 and N-Myc was used to analyze colocalization, and multiple cell function tests were performed by means of experiments to elucidate the functional role of TPX2 using RNA interference technology in NB cell lines. In both the TARGET-NB set and the validation set, it was found that upregulated of TPX2 was significantly associated with poor overall survival (OS) in patients with NB. The expression of TPX2 was higher in NB patients with MYCN gene amplification, and NB patients with high TPX2 expression and MYCN gene amplification had the poorest OS compared with patients with low TPX2 expression or a single copy of MYCN. experiments indicated that TPX2 positively regulated cell proliferation and the cell cycle, and promoted cell survival by increasing the resistance to apoptosis. The colocalization of TPX2 with N-Myc in NB cells and tissue was observed. The findings of the present study indicate that TPX2 plays an oncogenic role in NB development and may be a potential prognostic indicator in patients with NB.
驱动蛋白样蛋白2靶向蛋白（TPX2）在多种肿瘤中表达上调，多项研究已证实TPX2作为癌症预后标志物的作用。然而，TPX2在神经母细胞瘤（NB）中的功能尚未完全阐明。在本研究中，对TPX2在NB中的临床意义和功能作用进行了研究。使用了治疗应用研究以生成有效治疗方法（TARGET）-NB数据集。本研究共纳入43例NB患者作为验证集。在评估TPX2的预后作用后，评估了TPX2与MYCN原癌基因bHLH转录因子（MYCN）基因扩增的联合预测效果。采用TPX2和N-Myc双免疫荧光染色分析共定位情况，并通过实验利用RNA干扰技术在NB细胞系中进行多种细胞功能测试以阐明TPX2的功能作用。在TARGET-NB集和验证集中均发现，TPX2表达上调与NB患者较差的总生存期（OS）显著相关。TPX2在MYCN基因扩增的NB患者中表达较高，与TPX2低表达或MYCN单拷贝的患者相比，TPX2高表达且MYCN基因扩增的NB患者OS最差。实验表明，TPX2正向调节细胞增殖和细胞周期，并通过增加对凋亡的抗性促进细胞存活。观察到TPX2与N-Myc在NB细胞和组织中的共定位。本研究结果表明，TPX2在NB发生发展中起致癌作用，可能是NB患者潜在的预后指标。
