The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
Department of Urology, The First People's Hospital of Linping District of Hangzhou, Hangzhou, China.
Medicine (Baltimore). 2024 May 17;103(20):e37939. doi: 10.1097/MD.0000000000037939.
Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC).
We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC.
The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells.
ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.
先前的研究表明 NEK2 在控制细胞周期方面具有关键作用，而细胞周期与多种肿瘤类型的预后不良有关，但针对透明细胞肾细胞癌（ccRCC）的研究较少。
我们从基因表达综合数据库（GEO）和 TCGA 数据库下载了临床数据，以及转录组和突变数据集。从 TCGA-KIRC 队列中提取与 NEK2 强共表达的基因，并提交给基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行功能分析。根据 NEK2 水平，研究患者的生存状态、突变特征、对免疫治疗的反应和对药物的敏感性。使用 GEPIA、TIMER 和 TISIDB 数据库检查 NEK2 水平与免疫细胞状态和免疫细胞浸润之间的潜在相关性。通过双免疫荧光（IF）实验鉴定 ccRCC 中 NEK2 的过表达及其与 CD8 的关系。
NEK2 基因在 ccRCC 中过表达，并增强核分裂和细胞周期活性。NEK2 表达水平高的 ccRCC 患者临床结局较差，突变负担较高，治疗反应较好。此外，NEK2 基因过表达与各种免疫细胞标志物集呈正相关，这也在验证队列中得到了证实，并且更多的免疫细胞浸润。
NEK2 高表达的 ccRCC 患者预后较 NEK2 低表达的患者差，这是由于其促进增殖的功能所致，同时伴有 CD8+T 细胞和 Tregs 浸润增加以及 T 细胞耗竭，并且对适当的治疗反应更好。
