Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551 Japan; Department of Pathology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, 737-8505 Japan.
Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551 Japan.
Hum Pathol. 2019 Feb;84:8-17. doi: 10.1016/j.humpath.2018.09.001. Epub 2018 Sep 18.
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Spheroid colony formation is a useful method to identify cancer stem cells (CSCs). The aim of this study was to identify a novel prognostic marker or therapeutic target for GC using a method to identify CSCs. We analyzed the microarray data in spheroid body-forming and parental cells and focused on the CLSPN gene because it is overexpressed in the spheroid body-forming cells in both the GC cell lines MKN-45 and MKN-74. Quantitative reverse-transcription polymerase chain reaction analysis revealed that CLSPN messenger RNA expression was up-regulated in GC cell lines MKN-45, MKN-74, and TMK-1. Immunohistochemistry of claspin showed that 94 (47%) of 203 GC cases were positive. Claspin-positive GC cases were associated with higher T and N grades, tumor stage, lymphatic invasion, and poor prognosis. In addition, claspin expression was coexpressed with CD44, human epidermal growth factor receptor type 2, and p53. CLSPN small interfering RNA treatment decreased GC cell proliferation and invasion. These results indicate that the expression of claspin might be a key regulator in the progression of GC and might play an important role in CSCs of GC.
胃癌（GC）是全球癌症相关死亡的主要原因之一。球体集落形成是鉴定癌症干细胞（CSC）的一种有用方法。本研究旨在通过鉴定 CSC 的方法，鉴定 GC 的新型预后标志物或治疗靶点。我们分析了球体形成体和成体细胞中的微阵列数据，并集中研究 CLSPN 基因，因为它在 GC 细胞系 MKN-45 和 MKN-74 的球体形成细胞中过度表达。定量逆转录聚合酶链反应分析显示，CLSPN 信使 RNA 在 GC 细胞系 MKN-45、MKN-74 和 TMK-1 中表达上调。 claspin 的免疫组织化学显示，203 例 GC 病例中有 94 例（47%）为阳性。 claspin 阳性 GC 病例与较高的 T 和 N 分级、肿瘤分期、淋巴浸润和不良预后相关。此外，claspin 表达与 CD44、人表皮生长因子受体 2 和 p53 共表达。CLSPN 小干扰 RNA 处理可降低 GC 细胞的增殖和侵袭。这些结果表明，claspin 的表达可能是 GC 进展的关键调节剂，并可能在 GC 的 CSC 中发挥重要作用。
