Fujiki Yuto, Ishikawa Akira, Katsuya Narutaka, Shiwa Yuki, Fukui Takafumi, Kuraoka Kazuya, Sudo Takeshi, Tazuma Sho, Ishii Yasutaka, Oka Shiro, Yasui Wataru, Mii Shinji
Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Diagnostic Pathology, National Hospital Organization (NHO), Kure Medical Center, and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan.
Med Mol Morphol. 2025 Apr 28. doi: 10.1007/s00795-025-00438-y.
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.
胰腺导管腺癌（PDAC）是最广为人知的癌症类型之一，其5年生存率一直很低。我们之前报道过MCM4是一种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例PDAC样本中MCM4的表达。利用RNA干扰技术在PDAC细胞系中研究了MCM4在PDAC中的功能作用。此外，通过下载6例PDAC病例的数据进行了单细胞分析。在免疫组织化学检测中，81例PDAC病例中有42例（51.9%）观察到MCM4高表达。MCM4阳性的PDAC与较高的pN分级显著相关。此外，MCM4高表达与显著较差的预后相关，并且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的细胞位于轨迹上游，其中一个簇与KIFC1相关，据报道KIFC1与癌症干性有关。这些结果表明MCM4表达在PDAC中的重要性及其与癌症干性的关联。
