Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer

Katsuya N.a· Ishikawa A.a· Kido A.a· Fukui T.a· Kobayashi G.b· Sekino Y.a· Uraoka N.b· Babasaki T.a· Yasui W.a· Sentani K.Oue N.a

Author affiliations

aDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
bDepartment of Pathology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, Japan

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Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: April 27, 2022
Accepted: June 04, 2022
Published online: July 13, 2022

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 3

ISSN: 1015-2008 (Print)
eISSN: 1423-0291 (Online)

For additional information: https://www.karger.com/PAT

Abstract

Introduction: Gastric cancer (GC) is a leading cause of cancer-related death worldwide. This study focused on minichromosome maintenance 4 (MCM4), a DNA helicase component that functions in DNA replication. Using spheroid colony formation, having a colony rich in cancer stem cells, this study aimed to investigate the clinicopathological importance of MCM4. Methods: We examined MCM4 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analysis in 10 and 113 GC cases, respectively. MCM4 function in GC was also investigated by RNA interference in GC cell lines. Results: In qRT-PCR and IHC analysis, high MCM4 expression was found in 60% and 83% of GC cases, respectively. MCM4-positive GC cases were significantly associated with higher T grade and tumor stage. Additionally, high MCM4 expression was significantly associated with poor prognosis and was an independent prognostic factor in multivariate analysis. MCM4 was significantly coexpressed with CD133, matrix metalloproteinase 7 (MMP7), epidermal growth factor (EGFR), and mesenchymal-epithelial transition factor (cMET). In GC cell lines, MCM4 knockdown affected cell growth and protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and EGFR pathways. Conclusion: These results indicate that MCM4 expression could be a key regulator in GC progression and is pivotal in treating GC.

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First-Page Preview

Abstract of Research Article

Received: April 27, 2022
Accepted: June 04, 2022
Published online: July 13, 2022

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 3

ISSN: 1015-2008 (Print)
eISSN: 1423-0291 (Online)

For additional information: https://www.karger.com/PAT

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