Inoue Satoshi, Tsunoda Takumi, Riku Miho, Ito Hideaki, Inoko Akihito, Murakami Hideki, Ebi Masahide, Ogasawara Naotaka, Pastan Ira, Kasugai Kunio, Kasai Kenji, Ikeda Hiroshi, Inaguma Shingo
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan.
Department of Pathology, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan.
Oncol Lett. 2020 Mar;19(3):1741-1750. doi: 10.3892/ol.2020.11290. Epub 2020 Jan 10.
Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein that is highly expressed in several types of malignant tumor, including malignant pleural mesothelioma, ovarian cancer and pancreatic adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN-1 monoclonal antibody identified a significant number of colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN-positive colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti-MSLN therapy. experiments using colon cancer cell lines were performed to investigate the biological significance of MSLN expression in tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet-like proliferation (P=0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04-4.91; P=0.039) as a potential risk factor. When comparing primary CRCs and the metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The experiments revealed a positive role for MSLN in colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN-positive CRC exhibiting metastasis could be targeted by anti-MSLN therapies.
间皮素（MSLN）是一种糖基磷脂酰肌醇（GPI）连接的细胞表面蛋白，在多种恶性肿瘤中高表达，包括恶性胸膜间皮瘤、卵巢癌和胰腺腺癌。最近，一项使用MN-1单克隆抗体的全面免疫组织化学研究发现了大量表达MSLN的结直肠癌肿瘤。然而，MSLN阳性结直肠癌患者的临床病理特征和生存情况尚未得到充分分析。在本研究中，通过免疫组织化学分析了270例原发性和44例转移性结直肠癌肿瘤中MSLN的表达，以确定MSLN免疫组织化学的临床实用性，并识别未来抗MSLN治疗的潜在候选者。使用结肠癌细胞系进行实验，以研究MSLN在肿瘤中表达的生物学意义。单因素分析结果显示MSLN表达与女性之间存在显著相关性（P=0.0042）。此外，还发现MSLN表达与实性/片状增殖之间呈负相关（P=0.014）。此外，MSLN弥漫性腔/膜表达的患者总生存期显著缩短（P=0.018）。多变量Cox风险回归分析显示弥漫性MSLN表达（风险比，2.26；95%置信区间，1.04-4.91；P=0.039）是一个潜在风险因素。比较原发性结直肠癌及其转移灶时，MSLN阳性（阳性细胞百分比）呈弱正相关（R=0.484；P<0.0001）。实验揭示了MSLN在结肠癌细胞增殖中的积极作用。因此，MSLN免疫组织化学可能有助于结直肠癌患者的预后评估。结果表明，大量发生转移的MSLN阳性结直肠癌患者可能是抗MSLN治疗的靶点。
