Zhang Bixi, Liu Peng, Li Yanchun, Hu Qing, Li Huan, Pang Xiaoyang, Wu Hao
Department of Pathology, Hunan Provincial People's Hospital, Hunan Normal University Changsha, Hunan, China.
Department of Gastroenterology, Third Xiangya Hospital, Central South University Changsha, Hunan, China.
Am J Cancer Res. 2022 Nov 15;12(11):4954-4976. eCollection 2022.
Kinesin family member 2C (KIF2C) is the best-characterized member of the kinesin-13 family and is involved in accurately fine-tuned dynamics of mitotic spindles. As KIF2C is involved in both spindle formation and regulation of DNA double-strand breaks, precise regulation of KIF2C is essential to prevent malignant transformation associated with gains and losses of DNA content. In the present study, we initially reviewed The Cancer Genome Atlas database and observed that KIF2C is abundantly expressed in most tumor types. We then analyzed the gene alteration profile, protein expression, prognosis, and immune reactivities of KIF2C in more than 10,000 samples from several well-established databases. In addition, we conducted a gene enrichment set analysis to investigate the potential mechanisms underlying the role of KIF2C in tumorigenesis. Multi-omics analysis of KIF2C demonstrated significant statistical correlations between KIF2C expression and clinical prognosis, oncogenic signature gene sets, myeloid-derived suppressor cell infiltration, ImmunoScore, immune checkpoints, microsatellite instability, and tumor mutational burden across multiple tumors. Single-cell data showed that KIF2C is abundantly expressed in malignant cells. The experimental validation demonstrated that KIF2C is highly expressed in gastric cancer cell lines, gastric adenocarcinoma, and hepatocelluar carcinoma. The findings of this study provide important insight for understanding the role and mechanisms of KIF2C in tumorigenesis and immunotherapy in a variety of cancers.
驱动蛋白家族成员2C(KIF2C)是驱动蛋白13家族中特征最明确的成员,参与有丝分裂纺锤体精确的动态微调。由于KIF2C参与纺锤体形成和DNA双链断裂的调控,因此对KIF2C进行精确调控对于预防与DNA含量增减相关的恶性转化至关重要。在本研究中,我们首先查阅了癌症基因组图谱数据库,发现KIF2C在大多数肿瘤类型中均大量表达。然后,我们分析了来自几个成熟数据库的10000多个样本中KIF2C的基因改变谱、蛋白表达、预后和免疫反应性。此外,我们进行了基因富集集分析,以研究KIF2C在肿瘤发生中作用的潜在机制。对KIF2C的多组学分析表明,在多种肿瘤中,KIF2C表达与临床预后、致癌特征基因集、髓系来源抑制细胞浸润、免疫评分、免疫检查点、微卫星不稳定性和肿瘤突变负荷之间存在显著的统计学相关性。单细胞数据显示KIF2C在恶性细胞中大量表达。实验验证表明,KIF2C在胃癌细胞系、胃腺癌和肝细胞癌中高表达。本研究结果为理解KIF2C在多种癌症的肿瘤发生和免疫治疗中的作用及机制提供了重要见解。