Luo Linjie, Li Ying, Zhang Lin, Yang Lijie
Department of Critical Care Medicine, Wenjiang District People's Hospital of Chengdu, Chengdu, Sichuan, China.
Department of Respiratory and Critical Care Medicine, Wenjiang District People's Hospital of Chengdu, Chengdu, Sichuan, China.
Technol Health Care. 2024;32(4):2277-2291. doi: 10.3233/THC-231058.
Lung adenocarcinoma (LUAD), a prevalent form of lung cancer, is characterized by its high global mortality rate. Previous studies have demonstrated the significance of Nucleoside diphosphate kinase (NME) in various cancers; however, the specific role of NME6 in LUAD remains inadequately understood.
This research aims to enhance our understanding of LUAD by investigating the expression level, epigenetic mechanism, signaling activities, and immune infiltrating characteristic immune cells of NME6 in patients.
The NME6 expression was explored between LUAD and normal tissue samples using GEPIA, UALCAN and HPA databases. The survival analysis was performed by Kaplan-Meier plotter. The Shiny Methylation Analysis Resource Tool was employed to examine the methylation characteristics of NME6. The Tumor Immune Single-cell Hub (TISCH) and CIBERSORT algorithm were utilized to analyze immune infiltrating characteristic immune cells between NME6 high- and low-expression group in LUAD.
According to GEPIA, UALCAN, and HPA databases, NME6 is highly expressed in LUAD compared to normal tissues. At the same time, elevated levels of NME6 were found to be significantly correlated with inferior overall survival outcomes in LUAD patients. Subsequently, the top 10 genes interacted with NME6 were mainly involved in seven pathways, such as p53 signaling pathway, glutathione metabolism, thiamine metabolism, metabolic pathways, and drug metabolism. Notably, NME6 methylation in LUAD samples was lower than in normal samples. The methylation of cg04625862 has a significant impact on the regulation of NME6 expression in LUAD. Furthermore, high NME6 expression in LUAD was associated with tumor stages and relative abundance of tumor infiltrating immune cells, such as Macrophage M2, activated mast cell, and neutrophil. Moreover, NME6 regulated the expression of m6A modification of genes related to LUAD, including METTL3, WTAP, RBM15B, METTL14, RBMX, VIRMA, YTHDC1, RBM15, ZC3H13, YTHDF1, YTHDC2, IGF2BP2, YTHDF3, HNRNPA2B1, YTHDF2, HNRNPC, FTO, and ALKBH5.
The analysis showed that NME6 is a crucial prognostic factor for LUAD patients. NME6 regulates genes related to m6A modification and immune cells infiltration. Furthermore, NME6 could sever as a potential therapeutic target for LUAD.
肺腺癌（LUAD）是肺癌的一种常见形式，其全球死亡率很高。先前的研究已经证明核苷二磷酸激酶（NME）在各种癌症中的重要性；然而，NME6在LUAD中的具体作用仍未得到充分了解。
本研究旨在通过调查NME6在患者中的表达水平、表观遗传机制、信号传导活性和免疫浸润特征性免疫细胞，来加深我们对LUAD的理解。
使用GEPIA、UALCAN和HPA数据库探索LUAD和正常组织样本之间的NME6表达。通过Kaplan-Meier绘图仪进行生存分析。使用Shiny甲基化分析资源工具检查NME6的甲基化特征。利用肿瘤免疫单细胞中心（TISCH）和CIBERSORT算法分析LUAD中NME6高表达组和低表达组之间免疫浸润特征性免疫细胞。
根据GEPIA、UALCAN和HPA数据库，与正常组织相比，NME6在LUAD中高表达。同时，发现LUAD患者中NME6水平升高与较差的总生存结果显著相关。随后，与NME6相互作用的前10个基因主要参与七个途径，如p53信号通路、谷胱甘肽代谢、硫胺素代谢、代谢途径和药物代谢。值得注意的是，LUAD样本中NME6的甲基化低于正常样本。cg04625862的甲基化对LUAD中NME6表达的调节有显著影响。此外，LUAD中NME6高表达与肿瘤分期以及肿瘤浸润免疫细胞如巨噬细胞M2、活化肥大细胞和中性粒细胞的相对丰度相关。此外，NME6调节与LUAD相关的基因的m6A修饰表达，包括METTL3、WTAP、RBM15B、METTL14、RBMX、VIRMA、YTHDC1、RBM15、ZC3H13、YTHDF1、YTHDC2、IGF2BP2、YTHDF3、HNRNPA2B1、YTHDF2、HNRNPC、FTO和ALKBH5。
分析表明NME6是LUAD患者的关键预后因素。NME6调节与m6A修饰和免疫细胞浸润相关的基因。此外，NME6可作为LUAD的潜在治疗靶点。
