Department of Respiratory, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Anticancer Drugs. 2022 Jan 1;33(1):e398-e408. doi: 10.1097/CAD.0000000000001220.
The Knl1-Mis12-Ndc80 (KMN) network genes (including KNL, MIS12 and NDC80 complexes) encode a highly conserved network of protein complexes that act in cell mitosis. In recent years, multiple studies revealed that KMN network genes also play a vital role in tumor appearance and growth. However, the role of the KMN gene network in non-small cell lung cancer (NSCLC) remains unknown. In this study, we analyzed the effects of KMN genes expression and clinical phenotype in patients with lung adenocarcinoma (LUAD). The expression of KMN network genes and related clinical information was extracted from The Cancer Genome Atlas. The samples were classified into cluster I and II by consistent clustering. We analyzed the gene distribution by principal component analysis, and the potential risk characteristics were analyzed using the least absolute shrinkage and selection operator Cox regression algorithm. Univariate and multivariate Cox regression analyses were used to analyze the clinical information. The Database for Annotation, Visualization, and Integrated Discovery, Gene MANIA and gene set enrichment analysis were used to analyze function and correlation among genes of the KMN network. The expression levels of nine out of ten KMN genes were significantly up-regulated in LUAD and were associated with poor overall survival (OS). Higher expression of NDC80 and KNL1 was related to low OS in both univariate and multivariate analyses. According to two independent prognostic KMN network genes (KNL1 and NDC80), a risk signature was established to predict the prognosis of patients with LUAD. Additionally, the genes NDC80 and KNL1 were considerably enriched in pathways associated with signaling pathways, biological processes, and the cell cycle. The results indicate that KMN network genes are intimately related to lung adenocarcinoma. KMN network genes are involved in the malignant process of LUAD. Assessment of NDC80 and KNL1 might be helpful for prognostic stratification and treatment strategy development.
Knl1-Mis12-Ndc80（KMN）网络基因（包括 KNL、MIS12 和 NDC80 复合物）编码一个高度保守的蛋白质复合物网络，在细胞有丝分裂中发挥作用。近年来，多项研究表明，KMN 网络基因在肿瘤的发生和生长中也起着至关重要的作用。然而，KMN 基因网络在非小细胞肺癌（NSCLC）中的作用仍不清楚。在这项研究中，我们分析了 KMN 基因表达与肺腺癌（LUAD）患者临床表型的关系。从癌症基因组图谱中提取 KMN 网络基因的表达和相关临床信息。通过一致聚类将样本分为聚类 I 和聚类 II。我们通过主成分分析分析基因分布，使用最小绝对收缩和选择算子 Cox 回归算法分析潜在风险特征。使用单变量和多变量 Cox 回归分析来分析临床信息。使用数据库注释、可视化和综合发现、基因 MANIA 和基因集富集分析来分析 KMN 网络基因的功能和相关性。在 LUAD 中，十个 KMN 基因中有九个的表达水平显著上调，与总体生存（OS）不良相关。在单变量和多变量分析中，NDC80 和 KNL1 的高表达与 OS 低相关。根据两个独立的预后 KMN 网络基因（KNL1 和 NDC80），建立了一个风险特征来预测 LUAD 患者的预后。此外，基因 NDC80 和 KNL1 在与信号通路、生物过程和细胞周期相关的途径中显著富集。结果表明，KMN 网络基因与肺腺癌密切相关。KMN 网络基因参与 LUAD 的恶性进程。评估 NDC80 和 KNL1 可能有助于预后分层和治疗策略的制定。
