Research Paper Volume 14, Issue 24 pp 10027—10049
High MCM8 expression correlates with unfavorable prognosis and induces immune cell infiltration in hepatocellular carcinoma
- 1 Department of Critical Care Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang, China
- 2 Department of Hepatobiliary and Pancreatic Surgery, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan 442000, Hubei, China
- 3 Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang, China
Received: October 8, 2022 Accepted: December 9, 2022 Published: December 27, 2022
https://doi.org/10.18632/aging.204440How to Cite
Copyright: © 2022 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
HCC: hepatocellular carcinoma; MCM8: Mini-chromosome maintenance complex component 8; IHC: Immunohistochemistry; OS: Overall survival; RFS: Recurrence-free survival; TCGA: The Cancer Genome Atlas; GEO: the Gene Expression Omnibus; GO: the Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene Set Enrichment Analyses; ROC: Receiver operating characteristic; PFS: progression-free survival; DSS: disease-specific survival; PPI: protein-protein interaction; CDC7: cell division cycle 7; PRIM1: primase-DNA-polypeptide 1; AFP: Alpha-fetoprotein; AUC: Area under the curve; TNM: tumor-node-metastasis; aHR: adjusted Hazard ratio; CI: Confidence interval; DCA: decision curve analysis.