Expression Level and Prognostic Potential of MAP3K8 in Human Cancers Based on Data Mining

Abstract Background: MAPK kinase kinase 8 (MAP3K8) is a member of the MAP3K family with a major role in the regulation of the MAPK pathway and immune response. Differential expression of MAP3K8 is closely correlated with tumorigenesis. In this study, we used bioinformatics tools to explore expression level, prognostic values, and interactive networks of MAP3K8 in human cancers.Methods: Expression profile of MAP3K8 was analyzed using the Oncomine Platform, the Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. Survival analysis was evaluated via UALCAN, GEPIA, and DriverDBv3 databases. Then, MAP3K8 related functional networks were explored within GeneMANIA and Cytoscape. Moreover, Metascape was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.Results: We found that MAP3K8 was down-expressed in most cancer samples compared with paired normal tissues. Results from databases revealed that high MAP3K8 expression was associated with poorer prognosis of OS in kidney renal clear cell carcinoma (KIRC) (GEPIA: Log-rank p=0.006, HR=1.5; DriverDBv3: Log-rank p=1.68e-07, HR=2.21; UALCAN: p=0.002) and thymoma (THYM) (DriverDBv3: Log-rank p=0.011, HR=5.44; UALCAN: p=0.041). High MAP3K8 expression was correlated with better prognosis of OS in mesothelioma (MESO) (GEPIA: Log-rank p=0.016, HR=0.56; DriverDBv3: Log-rank p=0.002, HR=0.46) and skin cutaneous melanoma (SKCM) (GEPIA: Log-rank p=0.00092, HR=0.64; UALCAN: p=0.017). Gene regulation network suggested that MAP3K8 was mainly involved in immune cell function and MAPK signaling pathway. Conclusions: MAP3K8 overexpression was correlated with improved survival in MESO and SKCM, and with damaged survival in KIRC and THYM, reemphasizing the potential for identifying predictive biomarkers and therapeutic targets focused on MAP3K8 and the MAPK pathway.