Zhou Xunjian, Nie Hui, Wang Chunrong, Yu Xiaoqian, Yang Xuejie, He Xiaoyun, Ou Chunlin
Department of Pathology, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), Changsha 410013, Hunan, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
J Cancer. 2024 Apr 15;15(10):3154-3172. doi: 10.7150/jca.90197. eCollection 2024.
Never in mitosis gene A-related kinase (NEK) is an 11-membered family of serine/threonine kinases (NEK1-NEK11), which are known to play important roles in the formation and development of cancer. However, few studies have examined the roles of these kinases in the development of stomach adenocarcinoma (STAD). In this study, we conducted a comprehensive analysis of the relationships between the NEKs family members and STAD. The differential expression of the genes in STAD was validated using The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases, and their prognostic and diagnostic values of NEKs in STAD were assessed using the Kaplan-Meier plotter and TCGA data. The effect of NEK expression on immune cell infiltration in STAD was analysed using the TIMER and TISIDB databases. The expression levels of the majority of the NEK family members were consistently upregulated in STAD, whereas that of NEK10 was downregulated. The upregulation of NEK2/3/4/5/6/8 was closely associated with clinicopathological parameters of patients, and the overexpressed levels of these proteins had good diagnostic value for the disease. NEK1/8/9/10/11 expression correlated with poor overall survival and post-progressive survival, whereas a higher NEK1/6/9/11 level implied worse first progressive survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the NEKs may be related to immunological responses. Additionally, our study confirmed that these kinases correlated with immune cell infiltration and different immune infiltration subtypes in STAD. Our results suggest that NEK9 in particular has the potential to be used as a diagnostic and prognostic biomarker of STAD development and progression and an immune target for treatment of the disease. These findings expand our understanding of the biological functions of the NEK family members in STAD.
有丝分裂相关基因A激酶（NEK）是一个由11个丝氨酸/苏氨酸激酶成员组成的家族（NEK1-NEK11），已知其在癌症的形成和发展中发挥重要作用。然而，很少有研究探讨这些激酶在胃腺癌（STAD）发展中的作用。在本研究中，我们对NEK家族成员与STAD之间的关系进行了全面分析。使用癌症基因组图谱（TCGA）和肿瘤免疫评估资源（TIMER）数据库验证了STAD中这些基因的差异表达，并使用Kaplan-Meier绘图仪和TCGA数据评估了NEK在STAD中的预后和诊断价值。使用TIMER和TISIDB数据库分析了NEK表达对STAD中免疫细胞浸润的影响。大多数NEK家族成员的表达水平在STAD中持续上调，而NEK10的表达水平下调。NEK2/3/4/5/6/8的上调与患者的临床病理参数密切相关，这些蛋白的过表达水平对该疾病具有良好的诊断价值。NEK1/8/9/10/11的表达与较差的总生存期和进展后生存期相关，而较高的NEK1/6/9/11水平意味着较差的首次进展生存期。基因本体论和京都基因与基因组百科全书富集分析表明，NEK可能与免疫反应有关。此外，我们的研究证实这些激酶与STAD中的免疫细胞浸润和不同的免疫浸润亚型相关。我们的结果表明，特别是NEK9有潜力用作STAD发展和进展的诊断和预后生物标志物以及该疾病治疗的免疫靶点。这些发现扩展了我们对NEK家族成员在STAD中生物学功能的理解。
