Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Pathology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, Japan.
Pathobiology. 2023;90(3):147-154. doi: 10.1159/000525590. Epub 2022 Jul 13.
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.
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.
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.
These results indicate that MCM4 expression could be a key regulator in GC progression and is pivotal in treating GC.
胃癌（GC）是全球癌症相关死亡的主要原因。本研究专注于微小染色体维持蛋白 4（MCM4），它是一种 DNA 解旋酶组件，在 DNA 复制中发挥作用。通过球体集落形成实验，我们旨在研究 MCM4 的临床病理重要性，该实验中集落富含癌症干细胞。
我们分别使用定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）分析检测了 10 例和 113 例 GC 病例中的 MCM4 表达。通过 RNA 干扰在 GC 细胞系中研究了 MCM4 在 GC 中的功能。
在 qRT-PCR 和 IHC 分析中，分别有 60%和 83%的 GC 病例中发现高 MCM4 表达。MCM4 阳性 GC 病例与较高的 T 分级和肿瘤分期显著相关。此外，高 MCM4 表达与预后不良显著相关，并且是多变量分析中的独立预后因素。MCM4 与 CD133、基质金属蛋白酶 7（MMP7）、表皮生长因子（EGFR）和间质上皮转化因子（cMET）显著共表达。在 GC 细胞系中，MCM4 敲低影响细胞生长和蛋白激酶 B（Akt）、细胞外信号调节激酶（ERK）和 EGFR 通路。
这些结果表明，MCM4 表达可能是 GC 进展的关键调节剂，在治疗 GC 中至关重要。
