Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan; Center for One Medicine Innovative Translational Research; COMIT, Gifu University, Gifu, Japan.
Pathol Res Pract. 2024 Apr;256:155263. doi: 10.1016/j.prp.2024.155263. Epub 2024 Mar 11.
IZUMO2 belongs to the testis-expressed IZUMO family of proteins, which are characterized by an N-terminal IZUMO domain. Based on integrated analysis of expression profiles and matched DNA methylation data from a public database, IZUMO2 represents a prognosis-related methylation-driven gene in colorectal cancer. However, it remains unclear whether IZUMO2 protein expression is suppressed or overexpressed in colorectal cancer cells. In this study, we aimed to elucidate the expression of the IZUMO2 protein in colorectal cancer, with a focus on the clinicopathological features. Sixty-four colorectal cancer tissue specimens were immunohistochemically stained using specific antibodies against IZUMO2. IZUMO2 immunoreactivity was detected at the invasion front in 30 of the 64 colorectal cancer samples. Kaplan-Meier analysis demonstrated that patients with IZUMO2 immunoreactivity had a relatively shorter overall and progression-free survival (log-rank test, P = 0.046 and 0.019, respectively). IZUMO2 immunoreactivity served as an independent factor predictive of poor progression-free survival in colorectal cancer (P = 0.025) as determined via the Cox proportional hazard regression model. Moreover, IZUMO2 immunoreactivity represented an independent factor for poor overall survival (P = 0.035) and progression-free survival (P = 0.013) in patients with colon cancer. The present findings suggest that IZUMO2 is expressed in many colorectal cancers, especially at the cancer invasion front, and may represent an indicator of poor prognosis in colorectal cancer.
IZUMO2 属于睾丸表达的 IZUMO 蛋白家族，其特征是具有 N 端 IZUMO 结构域。基于公共数据库中表达谱和匹配的 DNA 甲基化数据的综合分析，IZUMO2 是结直肠癌中与预后相关的甲基化驱动基因。然而，IZUMO2 蛋白在结直肠癌细胞中的表达是受抑制还是过表达仍不清楚。在这项研究中，我们旨在阐明 IZUMO2 蛋白在结直肠癌中的表达情况，重点关注其临床病理特征。使用针对 IZUMO2 的特异性抗体对 64 例结直肠癌组织标本进行免疫组织化学染色。在 64 例结直肠癌样本中，有 30 例在肿瘤侵袭前沿检测到 IZUMO2 免疫反应性。Kaplan-Meier 分析表明，具有 IZUMO2 免疫反应性的患者总体生存率和无进展生存率相对较短（对数秩检验，P=0.046 和 0.019）。通过 Cox 比例风险回归模型，IZUMO2 免疫反应性被确定为结直肠癌无进展生存率的独立预后不良因素（P=0.025）。此外，IZUMO2 免疫反应性是结肠癌患者总体生存率（P=0.035）和无进展生存率（P=0.013）不良的独立因素。这些发现表明，IZUMO2 在许多结直肠癌中表达，尤其是在肿瘤侵袭前沿，可能是结直肠癌预后不良的指标。
