The prognostic value of mitogen-activated protein kinase kinase in liver hepatocellular carcinoma by bioinformatics

Liver hepatocellular carcinoma (LIHC) is a common cancer worldwide. Mitogen-activated protein kinase kinase (MAP2Ks) are related to the occurrence and development of a variety of tumors. However, the expression pattern, role, and prognostic value of the 7 MAP2K family members in LIHC have not yet been elucidated. We used the Oncomine, UALCAN, Human Protein Atlas, GeneMANIA, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, TIMER, and Kaplan-Meier Plotter databases. On August 7, 2021, we searched these databases for the terms MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, and "liver cancer." The exposure group comprised LIHC patients, and the control group comprised normal patients (those with noncancerous liver tissue). All patients shown in the retrieval language search were included. We compared the mRNA expression of these proteins in LIHC and control patients to examine the potential role of MAP2K1 to 7 in LIHC. Relative to the normal liver tissue, mRNA expression of MAP2K1/3 was significantly downregulated (P < .001), MAP2K4 was downregulated (P < .05), and that of MAP2K2/5/6/7 significantly upregulated (P < .001), in LIHC. MAP2K mRNA expression varied with gender (P < .0001), cancer stage (P < .05), tumor grade (P < .05), and with node metastasis status (P < .05), except for MAP2K4. Based on Kyoto Encyclopedia of Genes and Genomes enrichment analysis, these genes were associated with the following pathways: MAPK signaling pathway, GnRH signaling pathway, Fc epsilon RI signaling pathway (P < .05). The MAP2Ks were significantly associated with purity (P < .05), except for MAP2K1/2, with B cell (P < .05), except for MAP2K3, and that all significantly associated withCD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration (P < .05). High mRNA expression of MAP2K1/3/4/5 (P < .05) and low expression of MAP2K6 (P < .05) indicated overall survival, the high expression of MAP2K3/4/5 were related to relapse free survival and progression free survival; the high expression of MAP2K3/5/7 were related to disease free survival. We identified MAP2K1 to 7 as potential diagnostic markers, and MAP2K2 to 7 as prognostic markers, of LIHC. Our future work will promote the use of MAP2Ks in the diagnosis and treatment of LIHC.