High MCM8 expression correlates with unfavorable prognosis and induces immune cell infiltration in hepatocellular carcinoma

Aging (Albany NY). 2022 Dec 27;14(24):10027-10049. doi: 10.18632/aging.204440. Epub 2022 Dec 27.

Abstract

Background: MCM8 has been reported highly expressed in several human malignancies. However, its role in HCC has not yet been researched.

Methods: The prognostic significance of MCM8 mRNA expression was analyzed using datasets from TCGA and GEO databases. Immunohistochemistry (IHC) assay was used to detect the MCM8 protein expression in HCC tissues. The Cox regression analysis was employed to determine the independent prognostic value of MCM8. Then, we established a nomogram for OS and RFS prediction based on MCM8 protein expression. We analyzed the DNA methylation and genetic alteration of MCM8 in HCC. Moreover, GO, KEGG and GSEA were utilized to explore the potential biological functions of MCM8. Subsequently, we evaluate the correlations between MCM8 expression and composition of the tumor microenvironment as well as immunocyte infiltration ratio in HCC.

Results: MCM8 mRNA and protein were significantly overexpressed in HCC tissues. High MCM8 protein expression was an independent risk factor for OS and RFS of HCC patients. MCM8 expression is altered in 60% of queried HCC patients. In addition, higher methylation of the CpG site cg03098629, cg10518808, and 17230679 correlated with lower MCM8 levels. MCM8 expression correlated with cell cycle and DNA replication signaling. Moreover, MCM8 may be correlated with different compositions of the tumor microenvironment and immunocyte infiltration ratio in HCC.

Conclusions: MCM8 was highly expressed in HCC tissues and was associated with poor prognosis. Meanwhile, high expression of MCM8 may induce immune cell infiltration and may be a promising prognostic biomarker for HCC.

Keywords: DNA methylation; MCM8; genetic alteration; hepatocellular carcinoma; immune infiltrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Cell Division
  • Humans
  • Liver Neoplasms* / genetics
  • Minichromosome Maintenance Proteins
  • Nomograms
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • MCM8 protein, human
  • Minichromosome Maintenance Proteins