Zhao Zheng, Wang Zheng, Bao Zhao-Shi, Gao Wei-Zhen, Zhang Yuan-Da, Ruan Ci-Jie, Lv Tao, Wang Yong, Sun Li-Hua
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Genet. 2021 May 3;12:646929. doi: 10.3389/fgene.2021.646929. eCollection 2021.
In glioma, kinesin family member 23 (KIF23) is up-regulated and plays a vital role in oncogenesis. However, the mechanism underlying KIF23 overexpression in malignant glioma remains to be elucidated. This study aims to find potential causes of KIF23 high expression at genome level. To clarify this issue, we obtained point mutation and copy number alterations (CNAs) of KIF23 in 319 gliomas using whole-exome sequencing. Only two glioma samples with missense mutations in KIF23 coding region were identified, while 7 patients were detected with amplification of KIF23. Additional analysis showed that KIF23 amplification was significantly associated with higher expression of KIF23. Gene ontology analysis indicated that higher copy number of KIF23 was associated TNF-α signaling pathway and mitotic cell circle checkpoint, which probably caused by subsequent upregulated expression of KIF23. Moreover, pan-cancer analysis showed that gaining of copy number was significantly associated with higher expression of KIF23, consolidating our findings in glioma. Thus, it was deduced that elevated KIF23 expression in glioma tended to be caused by DNA copy number amplification, instead of mutation.
在胶质瘤中，驱动蛋白家族成员23（KIF23）表达上调，并在肿瘤发生中起重要作用。然而，恶性胶质瘤中KIF23过表达的潜在机制仍有待阐明。本研究旨在从基因组水平寻找KIF23高表达的潜在原因。为了阐明这一问题，我们通过全外显子测序获得了319例胶质瘤中KIF23的点突变和拷贝数改变（CNA）。仅鉴定出2例KIF23编码区存在错义突变的胶质瘤样本，而7例患者检测到KIF23扩增。进一步分析表明，KIF23扩增与KIF23的高表达显著相关。基因本体分析表明，KIF23拷贝数增加与肿瘤坏死因子-α（TNF-α）信号通路和有丝分裂细胞周期检查点相关，这可能是由于KIF23表达上调所致。此外，泛癌分析表明，拷贝数增加与KIF23的高表达显著相关，巩固了我们在胶质瘤中的研究结果。因此，推断胶质瘤中KIF23表达升高倾向于由DNA拷贝数扩增而非突变引起。
