NME6 as a potential biomarker and therapeutic target involved in immune infiltration for lung adenocarcinoma

Article type: Research Article

Authors: Luo, Linjie^{a; 1} | Li, Ying^{b; 1} | Zhang, Lin^{b; 1} | Yang, Lijie^{c; *}

Affiliations: [a] Department of Critical Care Medicine, Wenjiang District People’s Hospital of Chengdu, Chengdu, Sichuan, China | [b] Department of Respiratory and Critical Care Medicine, Wenjiang District People’s Hospital of Chengdu, Chengdu, Sichuan, China | [c] Prevention and Treatment Center, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China

Correspondence: [*] Corresponding author: Lijie Yang, Prevention and Treatment Center, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. E-mail: drlijieyang@163.com.

Note: [1] These authors share the first authorship.

Abstract: BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Keywords: Nucleoside diphosphate kinase 6, lung adenocarcinoma, DNA methylation, survival analysis, immune infiltration, m6A modification

DOI: 10.3233/THC-231058

Journal: Technology and Health Care, vol. 32, no. 4, pp. 2277-2291, 2024