Prognostic Value and Therapeutic Potential of NEK Family in Stomach Adenocarcinoma

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.