Object: Maternal embryonic leucine zipper kinase (MELK) is involved in the development and progression of various cancers. This work investigated the usefulness of MELK in the prediction of hepatocellular carcinoma (HCC) prognosis.

Methods: Information on MELK expression was obtained by pan-cancer analysis using The Cancer Genome Atlas (TCGA) database. The TCGA-liver hepatic cancer (TCGA-LIHC), Oncomine datasets, International Cancer Genome Consortium (ICGC) datasets were used to investigate MELK expression in HCC. The prognostic roles of MELK in HCC were assessed by univariate and multivariate survival analyses. The underlying mechanism for noncoding RNAs (ncRNAs) involved in MELK expression was investigated by in silico studies, correlation, methylation, and survival analyses. The relationships between MELK expression and immune cells, immune markers, and checkpoint markers were also analyzed.

Results: (1) MELK was identified as an independent predictor of overall survival (OS) in HCC patients (MELK high vs. low expression, HR 2.469; 95% CI 1.217–5.008; p = 0.012) in a multivariate Cox analysis, with a concordance index (C-index) value of 0.727 (95% CI 0.750–0.704). (2) The noncoding RNA miR3142HG and the LINC00265/has-miR-101-3p axis were found to regulate MELK expression in HCC tissue. (3) MELK levels were linked to various immune functions, including tumor infiltration and the expression of immune checkpoints and biomarkers in HCC.

Conclusion: MELK may have an oncogenic function in HCC and was found to be up-regulated by ncRNAs and associated with immune cell infiltration and unfavorable prognosis.