Immune modulation and prognostic significance of MCM10 in pan-cancer: a comprehensive analysis

Mostafa A Abdel-Maksoud; Komal Iqbal; Sanobar Gull; Sanjay Kirshan Kumar; Maryam Mastoor; Saeedah Musaed Almutairi; Taghreed N Almanaa; Akram A Alfuraydi; Ayman Mubarak; Mohamed H Kotob; Muhammad Jamil; Mohamed Y Zaky

Immune modulation and prognostic significance of MCM10 in pan-cancer: a comprehensive analysis

Am J Transl Res. 2023 Nov 15;15(11):6451-6463. eCollection 2023.

Affiliations

¹ Department of Botany and Microbiology, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Basic Health Unit Hindwan, Department of Primary Secondary Health Sahiwal, Sargodha 40210, Punjab, Pakistan.
³ Department of Biochemistry, Government College University Faisalabad Faisalabad, Pakistan.
⁴ Bahria University Health Sciences Karachi, Pakistan.
⁵ Department of Biochemistry, Amna Inayat Medical College Lahore, Pakistan.
⁶ Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna Vienna, Austria.
⁷ PARC Arid Zone Research Center Dera Ismail Khan 29050, Pakistan.
⁸ UPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Pittsburgh, PA 15213, USA.

PMID: 38074804
PMCID: PMC10703649

Abstract

Background: Oncogenic processes in cancer are often characterized by dysregulation of critical genes. Our study focused on the minichromosome maintenance 10 replication initiation factor (MCM10) gene's expression and its potential diagnostic and prognostic implications in pan-cancer.

Method: Leveraging large-scale genomic datasets, and experimental validation we embarked on a comprehensive analysis to shed light on the diagnostic and prognostic role of MCM10.

Results: Our findings underscore the wide-ranging up-regulation of MCM10 across 24 major cancer types, positioning it as a ubiquitous player in tumorigenesis. Significantly, MCM10 up-regulation was strongly associated with poorer overall survival in Kidney Renal Papillary Cell Carcinoma (KIRP), Liver Hepatocellular Carcinoma (LIHC), and Lung Adenocarcinoma (LUAD), emphasizing its potential as a valuable prognostic marker in these cancers. While genetic mutations often drive oncogenic processes, our mutational analysis revealed the relative stability of MCM10 in KIRP, LIHC, and LUAD. This suggests that epigenetic (hypomethylation) and non-mutational regulatory mechanisms predominantly govern MCM10 expression in these cancer types. Further analyses demonstrated positive correlations between MCM10 expression and immune cell infiltration, particularly CD8+ T cells and CD4+ T cells, offering insights into the gene's influence on the tumor immune microenvironment. Additionally, pathway enrichment analysis highlighted MCM10-associated genes' involvement in crucial signaling pathways, such as the cell cycle, DNA replication, and repair. Exploring the therapeutic potential, we examined important drugs capable of regulating MCM10 expression, opening doors to personalized treatment strategies.

Conclusion: Our study elucidates the multifaceted roles of MCM10 in KIRP, LIHC, and LUAD. Its pervasive up-regulation, prognostic significance, epigenetic regulation, and influence on the immune microenvironment provide valuable insights into these cancers. This research contributes to the growing body of evidence surrounding MCM10 and invites further investigation, validation, and potential translational efforts to harness its clinical relevance.

Keywords: MCM10; cancer; diagnosis; prognosis.