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

Sep 23, 2026

Pancreatic ductal adenocarcinoma (PDAC) has persistently poor survival, and the role of minichromosome maintenance 4 (MCM4) in PDAC remains unclear despite prior reports linking MCM4 to cancer stem cells. MCM4 expression was assessed in 81 PDAC samples by immunohistochemistry, and its functional impact was tested via RNA interference in PDAC cell lines. Single-cell analysis used data from six PDAC cases to map MCM4-expressing populations.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Keywords

Introduction

Background on PDAC prognosis and therapy resistance

Cancer stem cells and molecular markers

Rationale for studying MCM4

Materials and Methods (partial)

Primary antibodies for immunohistochemistry and western blot

Medical Molecular Morphology (2026) 59:8–19 [https://doi.org/10.1007/s00795-025-00438-y](https://doi.org/10.1007/s00795-025-00438-y) Minichromosome maintenance 4 is associated with poor survival and stemness of patients with pancreatic cancer Yuto Fujiki1 · Akira Ishikawa1 · Narutaka Katsuya1 · Yuki Shiwa1 · Takafumi Fukui1 · Kazuya Kuraoka2 · Takeshi Sudo3 · ShoTazuma3 · Yasutaka Ishii4 · Shiro Oka4 · Wataru Yasui1,5 · Shinji Mii1 Received: 29 January 2025 / Accepted: 16 April 2025 / Published online: 28 April 2025 © The Author(s) 2025 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. Keywords Pancreatic cancer · MCM4 · Cancer stem cell · Molecular pathology · Single cell analysis Introduction Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy, with a dismal 5-year survival rate of just around 11%, despite recent advancements in * Akira Ishikawa [a-ishikawa@hiroshima-u.ac.jp](a-ishikawa@hiroshima-u.ac.jp) 1 Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan 2 Department of Diagnostic Pathology, National Hospital Organization (NHO), Kure Medical Center, and Chugoku Cancer Center, 3-1 Aoyama, Kure 737-0023, Japan 3 Department of Surgery, National Hospital Organization (NHO), Kure Medical Center, and Chugoku Cancer Center, 3-1 Aoyama, Kure 737-0023, Japan 4 Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan 5 Division of Pathology, Hiroshima City Medical Association Clinical Laboratory, 3 Chome-8-6 Sendamachi, Naka-ku, Hiroshima 730-8611, Japan understanding PDAC tumor biology and the development of novel therapies [1]. Although PDAC can take time to progress [2], making early detection relatively manageable for treatment [3], only approximately 10–20% of patients have resectable pancreatic cancer at diagnosis [1]. Chemotherapy remains the cornerstone of PDAC treatment. Although some patients experience substantial clinical benefits, therapeutic resistance prevails. This resistance highlights the resilience of pancreatic cancer and its remarkable ability to create a tumor-protective microenvironment [4]. Therefore, in PDAC treatment strategies, the development of additional molecular targeted therapies is highly desirable, and targeting a distinctive microenvironment is considered a promising approach. Targeting cancer stem cells (CSCs), a key component of the tumor microenvironment, offers a means of understanding their pathogenesis and identifying potential therapeutic targets. CSCs are believed to drive tum

FAQs

What was the main goal of the study about MCM4 in pancreatic cancer?

To determine whether MCM4 is associated with PDAC survival outcomes and cancer stemness, since its role in PDAC had not been reported previously.

How was MCM4 expression evaluated in PDAC patient samples?

MCM4 expression was analyzed in 81 PDAC samples using immunohistochemistry (IHC). High MCM4 expression was observed in 42 of 81 cases (51.9%).

What functional effects did MCM4 knockdown have in PDAC cell lines?

RNA interference–mediated MCM4 knockdown impaired cell growth and spheroid formation in PDAC cell lines.

Sep 23, 2026

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