Decoding the significant diagnostic and prognostic importance of maternal embryonic leucine zipper kinase in human cancers through deep integrative analyses.

Abstract

Cancer is a multifactorial disease and the second leading cause of human deaths worldwide. So far, the underlying mechanisms of cancer have not been yet fully elucidated. By using TCGA expression data, we determine the pathogenic roles of the maternal embryonic leucine zipper kinase (MELK) gene in various human cancers in this study. For this purpose, different online databases and tools (UALCAN, Kaplan-Meier (KM) plotter, TNMplot, GENT2, GEPIA, HPA, cBioPortal, STRING, Enrichr, TIMER, Cytoscape, DAVID, MuTarget, and CTD) were used. MELK gene expression was analyzed in a total of 24 human cancers and was found notably up-regulated in all the 24 analyzed tumor tissues relative to controls. Moreover, across a few specific cancers, including kidney renal clear cell carcinoma (KIRC), stomach adenocarcinoma (STAD), lung adenocarcinoma (LUAD), and liver hepatocellular carcinoma (LIHC) patients, MELK up-regulation was observed to be correlated with the shorter survival duration and metastasis. This valuable information highlighted that MELK plays a significant role in the development and progression of these four cancers. Based on clinical variables, MELK higher expression was also found in KIRC, STAD, LUAD, and LIHC patients with different clinical variables. Gene ontology and pathway analysis outcomes showed that MELK-associated genes notably co-expressed with MELK and belongs to a variety of diverse biological processes, molecular functions, and pathways. MELK expression was also correlated with promoter methylation levels, genetic alterations, other mutant genes, tumor purity, CD8+ T, and CD+4 T immune cells infiltrations in KIRC, STAD, LUAD, and LIHC. This pan-cancer study revealed the diagnostic and prognostic roles of MELK across four different cancers.