Minichromosome maintenance 4 is associated with poor survival and stemness of patients with pancreatic cancer.

IF 1.2 4区医学 Q3 PATHOLOGY

Medical Molecular Morphology Pub Date : 2025-04-28 DOI:10.1007/s00795-025-00438-y

Yuto Fujiki, Akira Ishikawa, Narutaka Katsuya, Yuki Shiwa, Takafumi Fukui, Kazuya Kuraoka, Takeshi Sudo, Sho Tazuma, Yasutaka Ishii, Shiro Oka, Wataru Yasui, Shinji Mii

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引用次数: 0

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most well-known cancer types, with a persistently poor 5-year survival rate. We previously reported MCM4 as a molecule associated with cancer stem cells; however, its role in PDAC has not been reported. Therefore, in this study, we aimed to fill this gap in the literature. We analyzed MCM4 expression in 81 PDAC samples using immunohistochemistry (IHC). The functional role of MCM4 in PDAC was investigated using RNA interference in PDAC cell lines. Additionally, a single-cell analysis was conducted by downloading data from six PDAC cases. On IHC, high MCM4 expression was observed in 42 out of 81 (51.9%) PDAC cases. MCM4-positive PDAC was significantly associated with a higher pN grade. Furthermore, high MCM4 expression was linked to a significantly poorer prognosis and was identified as an independent prognostic factor in multivariate analysis. In PDAC cell lines, MCM4 knockdown impairs cell growth and spheroid formation. Single-cell analysis also revealed that MCM4-expressing cells were located upstream of the trajectory, with a cluster showing a correlation with KIFC1, which has been reported to be associated with cancer stemness. These results indicated the significance of MCM4 expression in PDAC and its association with cancer stemness.

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小染色体维持与胰腺癌患者的低生存率和干细胞性相关。

胰腺导管腺癌（Pancreatic ductal adencarcinoma， PDAC）是最常见的癌症类型之一，其5年生存率一直很低。我们之前报道过MCM4是一个与癌症干细胞相关的分子；然而，其在PDAC中的作用尚未见报道。因此，在本研究中，我们旨在填补这一文献空白。我们使用免疫组织化学（IHC）分析了81个PDAC样本中MCM4的表达。采用RNA干扰法研究MCM4在PDAC中的功能作用。此外，通过下载6例PDAC病例的数据进行单细胞分析。在IHC中，81例PDAC患者中有42例（51.9%）MCM4高表达。mcm4阳性PDAC与较高的pN分级显著相关。此外，MCM4高表达与预后明显较差相关，并在多变量分析中被确定为独立的预后因素。在PDAC细胞系中，MCM4敲低会损害细胞生长和球体形成。单细胞分析还显示，表达mcm4的细胞位于轨迹的上游，其中一个簇显示与KIFC1相关，据报道，KIFC1与癌症干细胞有关。这些结果表明MCM4在PDAC中的表达及其与肿瘤干细胞的相关性。

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

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.