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

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2023-01-01 DOI:10.1159/000525590

Narutaka Katsuya, Akira Ishikawa, Aya Kido, Takafumi Fukui, Go Kobayashi, Yohei Sekino, Naohiro Uraoka, Takashi Babasaki, Wataru Yasui, Kazuhiro Sentani, Naohide Oue

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引用次数: 2

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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小染色体维持4与胃癌患者的癌症干细胞和不良生存率相关

胃癌(GC)是世界范围内癌症相关死亡的主要原因。本研究的重点是微染色体维持4 (MCM4)，这是一种DNA解旋酶成分，在DNA复制中起作用。本研究利用球形集落形成，具有丰富的肿瘤干细胞集落，旨在探讨MCM4的临床病理意义。方法:采用定量逆转录聚合酶链反应(qRT-PCR)和免疫组化(IHC)方法检测MCM4在10例和113例胃癌中的表达。用RNA干扰法研究了MCM4在GC细胞中的功能。结果:在qRT-PCR和IHC分析中，MCM4高表达分别在60%和83%的GC病例中发现。mcm4阳性胃癌患者与较高的T级及肿瘤分期显著相关。此外，MCM4高表达与预后不良显著相关，在多因素分析中是一个独立的预后因素。MCM4与CD133、基质金属蛋白酶7 (MMP7)、表皮生长因子(EGFR)和间充质上皮转化因子(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。结论:这些结果表明MCM4的表达可能是胃癌进展的关键调节因子，在胃癌的治疗中起关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.