School of the First Clinical College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
The Fifth Affiliated Hospital of Wenzhou Medical University& Lishui Municipal Central Hospital, Lishui, Zhejiang, China.
Int Immunopharmacol. 2023 Mar;116:109737. doi: 10.1016/j.intimp.2023.109737. Epub 2023 Feb 2.
Gastric cancer (GC) is the most common form of gastrointestinal cancer, with a high mortality rate and limited treatment options. High levels of NEK2 are associated with malignant progression and a poor prognosis in several tumors; however, the role of NEK2 in GC remains unclear. We aimed to explore the potential role of NEK2 in the oncogenesis of GC and in the shaping of the tumor microenvironment (TME). The expression levels of NEK2 were analyzed using immunohistochemistry and real-time quantitative polymerase chain reaction. We found that NEK2 expression was upregulated in GC and was a predictor of a poor prognosis. Based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment and gene set enrichment analyses, multiple tumor pathways were hyperactivated in patients with high NEK2 mRNA expression. Immunological characteristics indicated that NEK2 upregulation might lead to decreased immune cell infiltration and weakened immune activity in the cancer immunity cycle. Additionally, higher frequencies of amplifications and deletions were observed in the high NEK2 expression subpopulation. Based on the TME classification, patients with high expression of NEK2 were more susceptible to targeted therapy with drugs targeting the cell cycle and DNA replication. Following verification, a NEK2-derived genomic model reliably predicted the patient prognosis; A nomogram (radiation therapy, tumor/node/metastasis staging, and the NEK2-derived risk score) was used to better estimate an individual's survival probability. In summary, our findings indicate that NEK2 plays a vital role in the tumorigenesis of GC.
胃癌（GC）是最常见的胃肠道癌症，死亡率高，治疗选择有限。在几种肿瘤中，NEK2 水平升高与恶性进展和预后不良有关；然而，NEK2 在 GC 中的作用尚不清楚。我们旨在探讨 NEK2 在 GC 发生和肿瘤微环境（TME）形成中的潜在作用。采用免疫组织化学和实时定量聚合酶链反应分析 NEK2 的表达水平。我们发现，NEK2 在 GC 中表达上调，是预后不良的预测因子。基于京都基因与基因组百科全书（KEGG）通路富集和基因集富集分析，高 NEK2 mRNA 表达患者的多个肿瘤通路被过度激活。免疫特征表明，NEK2 的上调可能导致癌症免疫周期中免疫细胞浸润减少和免疫活性减弱。此外，在高 NEK2 表达亚群中观察到更高频率的扩增和缺失。根据 TME 分类，高 NEK2 表达的患者更容易对靶向细胞周期和 DNA 复制的药物进行靶向治疗。经过验证，基于 NEK2 的基因组模型能够可靠地预测患者的预后；使用列线图（放疗、肿瘤/淋巴结/转移分期和基于 NEK2 的风险评分）可以更好地估计个体的生存概率。总之，我们的研究结果表明，NEK2 在 GC 的发生中起关键作用。
